Devices and methods for accelerometer-based characterization of cardiac function and identification of lv target pacing zones

ABSTRACT

Systems according to the invention employ an acceleration sensor to characterize displacement and vibrational LV motion, and uses this motion data to characterize the different phases of the LV cycle for analyzing LV function. Systems may identify a target pacing region or regions in the LV or RV using the acceleration sensor by localizing regions of late onset of motion relative to the QRS, or isovolumic contraction, or mitral valve closure, or by pacing of target regions and measuring LV function in response to pacing. Systems further provide an implantable or non-implantable acceleration sensor device for measuring LV motion and characterizing LV function. An implantable myocardial acceleration sensing system (“IAD”) includes at least one acceleration sensor, a data acquisition and processing device, and an electromagnetic, e.g., RF, communication device. The IAD may be integrated into the pacing lead of a CRT device and can operate independently of the CRT IPG.

REFERENCE TO CONTINUING APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/318,325, filed Dec. 23, 2005, entitled “Devices and Methods ForAccelerometer-Based Characterization of Cardiac Function andIdentification of LV Target Pacing Zones, which claims the benefit ofU.S. Provisional Application No. 60/650,532, filed Feb. 7, 2005, U.S.Provisional Application No. 60/655,038, filed Feb. 22, 2005, U.S.Provisional Application No. 60/656,307, filed Feb. 25, 2005, U.S.Provisional Application No. 60/657,766, filed Mar. 1, 2005, U.S.Provisional Application No. 60/659,658, filed Mar. 8, 2005, U.S.Provisional Application No. 60/663,788, filed Mar. 21, 2005, U.S.Provisional Application No. 60/669,324, filed Apr. 7, 2005, U.S.Provisional Application No. 60/677,569, filed May 4, 2005 and U.S.Provisional Application No. 60/680,673, filed May 13, 2005. Each of theprior US Provisional Patent Applications is incorporated by reference inits entirety herein.

BACKGROUND

The human heart delivers oxygenated blood to the organs of the body tosustain metabolism. The human heart has four chambers, two atria and twoventricles. The atria assist with filling of the ventricles, which pumpblood to the body and through the lungs. The right ventricle (RV) pumpsblood through the lungs to be oxygenated and the left ventricle (LV)pumps the oxygenated blood to the body.

A graph of the cardiac filling and pumping cycle and valvular events isshown in FIGS. 1 a and 1 b. The cardiac LV pumping cycle (LV cycle) isdivided into two periods: diastole 52 and systole 54. Diastole 52 is thefilling period and systole 54 is the ejection period. Five differentphases of the LV cycle can be identified within the systolic anddiastolic periods: isovolumic contraction 56, ejection 58, isovolumicrelaxation 62, early diastolic filling (rapid filling) 64, and latediastolic filling (atrial contraction) 66. Mitral valve closure 68(“MVC”) occurs during isovolumic contraction and aortic valve closure 72(“AVC”) occurs during isovolumic relaxation. Also shown in the figuresare the left ventricular pressure LV Press 74, a regularelectrocardiogram ECG 76, the left ventricular end-diastolic volumeLVEDV 78, the left ventricular end-systolic volume LVESV 82, a graphdepicting heart sounds 84, the left atrial pressure LA Press 86, theaortic pressure 88, a-wave 92, c-wave 94, and v-wave 96.

Myocardial activation and systolic contraction is initiated in the atriaby a regular electrical depolarization wave that spreads from thesinoatrial node to the ventricles at a normal resting cycle of 60 to80/minute. Cardiac electrical activity can be sensed using a bodysurface electrocardiogram or ECG. The depolarization of the atria issensed as a P-wave 98 on the ECG. A delay in depolarization between theatria and ventricles occurs and is measured on the ECG as the PRinterval 102. Ventricular contraction and myocardial shortening startsat the interventricular septum and rapidly spreads to the posterior andlateral wall via the Purkinje system. Electrical depolarization thatleads to ventricular contraction is measured on the ECG by the QRScomplex 104. Following the QRS complex 104 is the T-wave 106, whichreflects ventricular repolarization.

In the normal heart, a short delay from interventricular septalcontraction to posterior-lateral contraction of approximately 20-40 msoccurs such that the lateral free wall is typically the first region ofthe heart to undergo shortening. Aortic valve closure signifies the endof the ejection phase of systole and the start of diastole. Diastoleresults in filling of the ventricles with blood and lengthening of themyocardium. In the normal heart diastole is typically longer thansystole with the ratio dependent on heart rate.

LV myocardial motion is complex and includes both vibration anddisplacement (lengthening and shortening). Displacement occurs primarilyalong the longitudinal axis (base to apex), but there is also someradial displacement as well as clockwise and counterclockwise rotation.Displacement of the entire heart can also be caused by respiration.Superimposed on the large amplitude displacement motion is low amplitudevibrational motion related to isovolumic contraction/relaxation, valveclosure, and valve pathologies such as mitral regurgitation.

The origin of LV displacement motion can be traced to the specificorientation and arrangement of muscle fibers in the myocardium.Vibrational motion of the LV is thought to be caused by acceleration anddeceleration of the blood and turbulent blood flow. Studies ofmyocardial architecture have shown that the fibers are situatedtransverse and diagonal in a helical pattern. Transverse circumferentialfibers are present in the base and midwall of the myocardium and produceradial narrowing of the ventricle. Systole starts with the developmentof tension primarily in the circumferential fibers, which stiffens andnarrows the ventricle, and causes primarily radial displacement. Thestart of systole coincides with the isovolumic contraction phase of theLV cycle and also causes a vibrational motion thought to be related todirectional changes of the blood and the accompanyingacceleration/deceleration. Mitral valve closure also occurs during thisisovolumic contraction period. Circumferential shortening is followed bylongitudinal-diagonal fiber shortening resulting in primarilylongitudinal displacement of the LV (base toward the apex) and ejectionof blood. The action of these fibers also creates a rotation of theheart. This coincides with the ejection phase of the LV cycle. Mitralregurgitation is prominent during this ejection phase. Followingejection, lengthening and rotation in the opposite direction begins, andthe isovolumic relaxation phase of the LV cycle occurs. Isovolumicrelaxation is also thought to be associated with vibrational motionrelated to the acceleration/deceleration of the blood. Aortic valveclosure also occurs during this phase. Early rapid filling of the LVwith blood, as well as late filling, causes radial and longitudinallengthening of the LV.

This motion of the ventricular myocardium and the LV cycle phases can bemeasured at the mitral annulus which is displaced radially andlongitudinally. In addition, some rotation and the vibrational motion istransmitted at the annulus. Longitudinal displacement is an integralpart of the global contractile function and has a good correlation withthe overall ejection performance and diastolic filling performance ofthe ventricle.

Heart failure or cardiomyopathy is a medical syndrome characterized bydeterioration of cardiac pumping performance. The primary deteriorationis a progressive loss of heart muscle compliance and contractility. Lossof pump function leads to cardiac dilation, blood volume overload,pulmonary congestion, and ultimately organ failure. Symptoms of heartfailure include orthopnea, dyspnea on exertion, cough, fatigue, andfluid retention. Many heart failure patients suffer from functionalmitral regurgitation that can worsen with exercise and contributes tothe progression of the disease. Lastly, patients with cardiomyopathy areprone to rhythm disturbances such as interventricular andintraventricular conduction delays leading to mechanical dyssynchrony,and tachyarrhythmias.

In cardiac pathology, such as heart failure, electrical conductionbetween atria and ventricles can be delayed excessively such thatpumping function of the heart deteriorates. In addition, conductiondelays in the spread of ventricular depolarization thwart the uniformspread of ventricular contraction and result in asynchronous ventricularshortening and a deterioration of performance. Some of the ventriculardepolarization delays are due to abnormalities of the Purkinje systemand are referred to as left or right bundle branch blocks (LBBB orRBBB). Bundle branch blocks are manifested by a wide QRS complex on theECG.

A prolonged QRS, often manifested as an LBBB in patients withcardiomyopathy, is associated with poor prognosis. In several largeclinical trials, lengthening of the QRS was independently associatedwith poor survival. In addition, several deleterious hemodynamicconsequences arise in the presence of bundle branch block includingshortening of the diastolic filling period, aggravation of mitralregurgitation, and abnormal systolic wall motion. The overall result isa typical and sometimes dramatic deterioration in cardiac performance.

Most therapies to improve cardiomyopathy are implemented and tailoredempirically, or indirectly, based on patient symptoms, with little or noinformation on the mechanical optimization of cardiac pumping. Inpractice, assessment of mechanical pumping properties is difficult. Someinformation can be obtained by inserting catheters into the chambers ofthe heart, but these catheters cannot be left in chronically and it isimpractical to subject patients to repeated procedures.

Objectives of cardiomyopathy therapy are to increase contractility,reduce afterload, i.e., the pressure against which the LV must pump,control blood and body water volume, blunt neurohumoral activation,improve cardiac compliance, increase ejection fraction, and reducemitral regurgitation. Drugs, medical devices, and surgical treatmentsare employed to accomplish these goals and include diuretic drugs, bloodpressure drugs, beta blocker drugs, cardiac pacing and resynchronizationwith or without tachyarrhythmia therapy, coronary artery bypassgrafting, and heart transplantation.

Pacemaker therapy to treat heart failure is an established medicaltherapy. This therapy is employed to correct the dyssynchronousmechanical activity that occurs in heart failure by controlling theelectrical activity of the heart. This form of pacing therapy is oftenreferred to as cardiac resynchronization therapy or CRT. Dual chamberpacing (right atrium and right ventricle) to improve atrioventricularsynchrony is a form of pacemaker therapy. Biventricular pacing is anewer approach that can improve cardiac function and mortality.Tachyarrhythmia and defibrillation therapy are also incorporated intothe pacing therapy as heart failure patients often have problems withtachyarrhythmia. An experimental implantable pacing therapy forcardiomyopathy is cardiac contractility modulation (“CCM”) in which avoltage potential or current is applied to the myocardium during thetissue's refractory period. This current improves myocardialcontractility.

CRT is achieved by pacing (inducing myocardial activation) in the RV andLV, and has assumed prominence in patients with advanced heart failureand refractory symptoms. Specific candidates include patients with aprolonged QRS duration >120 milliseconds and/or LBBB. In newerapproaches the RV and LV pacing is controlled and may occur at differentintervals. LV free wall pacing only is also being explored.

Most clinical trials have demonstrated that about two-thirds of patientswill have a clinical response to CRT as long as optimal pharmacologictherapy is maintained. Clinical responses include improvement in NewYork Heart Association functional class, improved exercise capacity, adecreased need for diuretic, reduced hospitalization for heart failuremanagement, and the like. Unfortunately, about one-third of patients donot respond, and approximately 15% of patients can actually have aworsened clinical outcome.

In biventricular pacing or CRT, cardiac leads are placed in the rightatrium (RA), the RV, and LV coronary veins via the coronary sinus. Theleads have electrodes that can sense cardiac electrical activity andstimulate contraction in the myocardium. The leads are connected to ahermetically sealed, battery powered, programmable pulse generator andsensor/data storage device, termed here an “IPG” that is implantedsubcutaneously.

Crucial to successful CRT is deployment of the left ventricular lead.This is typically accomplished by passing the LV lead through thecoronary sinus into one of its venous tributaries overlying theepicardial left ventricular surface. Conventional pacing target sitesare the posterior and lateral myocardium. In principle, the target siteshould be the segment of latest regional myocardial contraction relativeto the QRS or some other measurement of the start of ventricularcontraction. Although this is predicted to be in the posterior-lateralregion, the actual site tends to be rather variable and difficult topredict in the individual patient. One other criterion for employing CRTis the identification of myocardial regions that contract in thepost-systolic period, or in the period after aortic valve closure. Suchregions are sometimes referred to as myocardial contractility reserve,because these regions of myocardium can add or contribute to systolicejection if they can be forced to contract during systole. Pacing ofregions can induce contraction and shortening of these late-contractingregions so that they contribute to systole. Consequently, any patientwith a region of myocardium that contracts and deforms in thepost-systolic period are candidates for CRT, regardless of the QRSinterval.

Tissue Doppler and its corresponding myocardial velocity measurementhave been used to measure various mechanical properties of ventriclesand atria. Characterization of systolic and diastolic function can beperformed. In addition, tissue Doppler has been employed in theassessment of mitral regurgitation and ischemia.

Tissue Doppler velocity measurements can detect tissue velocity changes,but these changes do not necessarily correlate with ventricularshortening which is required for cardiac pumping during systole. In anasynchronous ventricle, contraction may not be accompanied by shorteningdue to the effects of earlier-contracting segments on late-contractingsegments. Newer techniques that employ measurements of cardiac strainand shortening are able to assess cardiac motion.

General strategies for LV lead placement can be developed with tissueDoppler imaging, a sophisticated echocardiographic technique, whichallows visualization of individual myocardial segments and theircontraction patterns, and allows visualization and analysis of segmentalwall motion and velocity. It has been observed that up to 50% ofpatients may have the left ventricular lead, when placed in aconventional fashion pacing in a zone that does not correspond to thebest myocardial contraction segment, i.e. there is a mismatch betweenthe desired target and the actual target. Moreover, it is only thosepatients in whom a match occurred between the paced segment and thetarget zone where a clinical response was observed (only in about 30-50%of patients). This may explain why there is a lower than desiredclinical response rate to CRT.

To improve CRT there is not only the need to identify target zones forpacing, but also to identify suitable patients. Further, a substantialpercentage of patients with a normal or only slightly-widened QRSinterval may also be candidates for CRT. Tissue Doppler scans can besuitable to measure ventricular dyssynchrony and therefore may be ableto identify appropriate patients and optimize therapy. One measure ofdyssynchrony identified with tissue Doppler is the assessment of peakvelocity delays relative to the QRS onset of different myocardialsegments and the standard deviation of these delays. However, tissueDoppler imaging requires specialists to perform the scan and can only beperformed during a clinical visit. Thus, continuous or daily monitoringis not possible with this technique. Moreover, the complexity of thetechnique makes it too cumbersome to use during the LV lead placement.

Motion of the heart and LV, both displacement and vibration, can bemeasured directly with an acceleration sensor. This motion can be usedto characterize the LV cycle phases. Integration of the accelerationmeasurements during displacement provides myocardial velocity data thatmay closely parallel tissue Doppler imaging velocity measurements.Double mathematical integration of the acceleration sensor signal wouldallow characterization of the distance of displacement. Thus, anacceleration sensor-based system could be used to identify targetregions of myocardium for pacing, optimize and characterize the regionaland global LV response to pacing of the target region, and identifycandidates for CRT, including those without a widened QRS. Since LVmotion and cardiac pathologies such as mitral regurgitation occur atdifferent frequencies, e.g., higher frequency vibration and lowerfrequency displacement, acceleration signals at different frequenciesare ascertained. In this way, the complete LV cardiac cycle and cardiacpathologies can be characterized and monitored for changes due topacing. An appropriately designed implantable myocardial accelerationsensing device (IAD) could monitor global and regional cardiac functionlong term, and would allow optimization of many treatment aspects ofheart failure, including pharmacologic therapy. This monitoring mayoccur without the need for specialized personnel and scanning. Moreover,the appropriately designed system would allow characterization of thecomplete cardiac cycle (systole and diastole) and global monitoring ofcardiac mechanical function.

Accelerometers have been used in pacemaker IPGs for rate controlpurposes (U.S. Pat. No. 5,383,473 and U.S. Pat. No. 5,425,750). A sensorimplanted in the heart mass for monitoring heart function by monitoringthe momentum or velocity of the heart mass is generally disclosed inU.S. Pat. No. 5,454,838. A catheter for insertion into the ventricle formonitoring cardiac contractility having an acceleration transducer at orapproximately at the catheter tip is generally disclosed in U.S. Pat.No. 6,077,236. Implantable leads incorporating accelerometer-basedcardiac wall motion sensors and for arrhythmia discrimination aregenerally disclosed in U.S. Pat. Nos. 5,628,777 and 6,002,963.Accelerometers used for discrimination of various cardiac arrhythmiasare also generally disclosed in U.S. Pat. No. 5,268,777. Additionally,other disclosures have proposed the use of an accelerometer to optimizepacing timing, such as AV delay/interval and interventricular (V-V)timing (U.S. Pat. Nos. 5,549,650; 6,542,775; 5,549,650, 5,540,727 andU.S. Applications 2003/0105496 A1, 2004/0172079 A1, 2004/0172078 A1, and2005/0027320 A1).

SUMMARY OF THE INVENTION

To the best of the inventor's knowledge none of the above disclosuresproposes using acceleration sensors to characterize all components of LVmotion, displacement and vibration, and to use this motion data tocharacterize the different phases of the LV cycle for analyzing LVfunction. These disclosures do not provide a means for separating outthe displacement and vibrational components of LV motion, which occur atthe same time, through different frequency sensing or filtering andanalysis. Prior disclosures do not provide devices or methods foridentifying the optimal myocardial pacing zone or region in the left orright ventricle for CRT, such as measuring the onset of motion relativeto the onset of the QRS or isovolumic contraction or mitral valveclosure. Prior disclosure do not provide a method for multiple catheterrepositionings in the LV or coronary sinus or great cardiac vein to mapthe motion of the LV for identifying the optimal pacing region. Priordisclosures do not describe characterizing the response to pacing of atarget region by measuring parameters indicative of r LV function (e.g.,myocardial performance index or QRS onset to aortic valve closure).Prior disclosures also do not disclose measuring cardiac pathologiessuch as mitral regurgitation, which may be sensed as vibration motion atfrequencies greater than about 150 Hz. Prior disclosures do not disclosea means for optimizing complete cardiomyopathy therapy, including drugsand devices, through the use of implantable acceleration devices. Priordisclosures do not provide a means for zeroing out gravity effects andtilt of the sensor. Prior disclosures do not define the use ofcapacitive acceleration sensors that integrate an inductive coil forwireless powering and data transmission.

Rather, prior disclosures typically describe a single accelerationsensor preferably disposed in the tip of an implantable pacing lead. Forexample, a single accelerometer is incorporated into the RV pacing leadto assess RV systolic activity and correlate the readings with RV dP/dt(“An implantable intracardiac accelerometer for monitoring myocardialcontractility”, PACE 1996, 19:2066-2071). The sensor is designed todetect only signals related to isovolumic contraction, and not themotion related to displacement or valvular pathologies. In anotherdisclosure, an accelerometer is incorporated into an LV pacing lead foroptimization of CRT timing intervals (US Application 2004/0172079 A1).This prior disclosure proposes to sense LV myocardial accelerationduring isovolumic contraction and use this information to optimize theatrioventricular delay and the interventricular delay pacing signals.There is no disclosure on the use of an acceleration sensor device toidentify target pacing regions and characterize the LV functionalresponse to pacing. There is no disclosure on a means for characterizingboth the displacement and vibration motion occurring at differentfrequencies. Consequently, the disclosure does not provide a way tomonitor information on phases of the LV cycle that characterize LVfunction such as, displacement related to ejection, filling, afterload,volume status, and preload, nor can the same characterize vibrationrelated to mitral regurgitation. Additionally, no disclosure is providedfor integrating the acceleration signal to yield LV displacementvelocity and distance measurements, which may provide additionalinformation on LV contractile function. Also, neither disclosure nordevice design is provided that would allow characterization ofmyocardial strain and strain rate.

In U.S. Patent Application 2003/015496 A1 single accelerometers areremoveably disposed at the tip of CRT leads in the LV, RV and RA. Atemporal phase shift between two different sensors is proposed tooptimize CRT interventricular timing. Similar to the above, thisdisclosure generally describes interventricular interval optimizationand does not provide a means for intraventricular target pacing regionidentification. Therefore it lacks disclosure on any means foridentifying LV pacing region, means for identifying LV response topacing, means for identifying LV dyssynchrony irrespective of QRS width,and characterization of LV motion and the phases of the LV cycle.Further, there is no disclosure for multi sensor integration into thesame lead catheter, guidewire, or guide catheter/catheter system, andanalysis of acceleration at different frequencies.

In one embodiment, the invention employs an acceleration sensor tocharacterize displacement and vibrational LV motion, and uses thismotion data to characterize the different phases of the LV cycle foranalyzing LV function. In another embodiment, the invention measuresacceleration in at least two different frequencies with either two ormore sensors or two or more frequency filters to characterize LV motion.In yet another embodiment, the invention senses high frequency (greaterthan about 150 Hz) low amplitude motion related to valvular pathology(e.g., mitral regurgitation), mid frequency (between about 20 Hz and 150Hz) lower amplitude motion related to isovolumic contraction/relaxationand valve closure, and low frequency (less than about 20 Hz) highamplitude motion signals related to displacement of the LV occurringduring the ejection phase and early and late diastole. In still afurther embodiment, the invention identifies a target pacing region orregions in the LV or RV using an acceleration sensor by localizingregions of late onset of motion relative to the QRS, or isovolumiccontraction, or mitral valve closure, or by pacing of target regions andmeasuring LV function in response to pacing. In another embodiment, theinvention measures myocardial motion with an accelerometer relative tothe onset of isovolumic relaxation or aortic valve closure to determinecontractile reserve and/or the presence of post-systolic shortening. Inyet another embodiment, the invention identifies target pacing regionsin the LV using an acceleration sensor by pacing different regions andmeasuring the regional and/or global LV functional response to pacing.In still a further embodiment, the invention uses an acceleration sensorto measure LV function by sensing changes in the time interval length ofthe LV cardiac cycle phases (isovolumic contraction/relaxation,ejection, and/or filling); changes in mitral regurgitation signalamplitude and duration; and changes in peak amplitude and slope ofisovolumic contraction, isovolumic relaxation, and ejection phases; andfrequency changes of the isovolumic contraction and relaxation phases.In another embodiment, the invention may use an acceleration sensor toidentify patients with LV dyssynchrony or asynchrony and a normal QRSwidth (90-120 ms), a modestly increased QRS width (120 to 150 ms), andwide QRS or LBBB pattern (QRS>150 ms). In yet another embodiment, theinvention facilitates identification of the coronary ostium and LV veinbranches into the coronary sinus for cannulation with guidewires orcatheters. In a still further embodiment, the invention provides thephysician with data from acceleration sensing for management of optimalpharmacologic treatment. In yet another embodiment, the inventionprovides a wireless acceleration sensing medical device and system forassessing LV motion and function.

Embodiments of the invention provide an implantable or non-implantableacceleration sensor device for measuring LV motion and characterizing LVfunction. An implantable myocardial acceleration sensing system (“IAD”)includes at least one acceleration sensor, a data acquisition andprocessing device, and an electromagnetic, e.g., RF, communicationdevice. The system may or may not have an internal battery.

In one embodiment, an IAD is integrated into the pacing lead of a CRTdevice and can operate independently of the CRT IPG. In anotherembodiment, an IAD is used without a CRT to monitor heart failure. Inthis embodiment, at least one sensor is incorporated into anendovascular catheter that can be placed in the epicardial venous systemof the LV.

In one illustrative system, the accelerometer sensors aremicro-electromechanically (“MEM”s)-based to allow miniaturization,low-power consumption, and multiple-axis sensing. The sensor areconductively attached to the subcutaneously-implanted data acquisitionand processing device, which is capable of RF telemetry communicationand data transfer. The IAD monitors both vibrational and displacement LVmotion during systole and diastole in at least the longitudinal axis.The IAD may also monitor LV acceleration in at least one location nearthe mitral annulus.

In another illustrative system, the IAD is integrated with a CRT devicewith a multi-electrode LV pacing lead. The IAD monitors LV motion andcan dynamically adjust the electrodes that are used to pace. Similarly,the IAD can be integrated with or used with a CCM device to help monitormechanical function and optimize therapy.

The IAD may perform data analysis algorithms that provide useful outputfor optimizing cardiomyopathy therapy. The output can be accessed by themultitude of physicians that are involved in cardiomyopathy management.These physicians include primary care physicians, internists,cardiologists, electrophysiologists, and cardiac surgeons. Statisticalanalysis of long-term data can identify periods in which cardiacfunction deviated significantly from baseline values or how the functionchanged with therapy.

IADs may also be implanted in the context of other cardiac proceduressuch as endovascular coronary procedures, electrophysiology procedures,coronary artery bypass grafting, and heart transplants. Thus, thepatient is not subjected to an additional procedure. Integration of anIAD with a CRT or CRT pacing lead similarly offers the opportunity tooptimize therapy and response in the context of a known and regularlyperformed procedure for cardiomyopathy.

In another embodiment, the sensor is a radiofrequency (“RF”) MEMsaccelerometer that incorporates coils that can inductively power orcharge the sensor and transmit the data. Such an RF sensor provides longterm, batteryless, wireless monitoring. Data from the wireless RF sensormay be acquired using an external antenna device that wirelessly couplesto the sensor by directing electromagnetic energy of the appropriatefrequency toward the sensor for inductive powering and/or datatransmission. The antenna device is connected to amicroprocessor-controlled display device that processes and stores themyocardial acceleration data for LV motion and therapy monitoring andoptimization.

In another embodiment, one or more RF sensors can be directly implantedinto or on the heart for LV motion or therapy monitoring or both.Alternatively, one or more RF sensors can be integrated into variousdevices that are implanted into the heart. In a further embodiment, oneor more RF sensors are integrated into an endovascular catheter that canbe inserted into the chambers or vessels of the heart. In anotherembodiment, one or more RF sensors are incorporated into a coronarystent. In still another embodiment, one or more RF sensors areincorporated into a cardiac pacing lead.

In still another embodiment, an LV motion mapping system is disclosedwhich can sense LV motion for optimizing CRT lead placement. The systemmay include an LV venous catheter, LV lead, guidewire, or guidecatheter/catheter system with an acceleration sensor, connected to asignal processing and powering module, and a graphical display. Theacceleration sensing catheter may be moved to different locations in theLV and used to identify regions of late systolic or post-systolic motionrelative to a reference point such as the QRS, valve closures, orisovolumic contraction/relaxation. Alternatively, a pacing catheter orguidewire may be moved to different LV locations and an accelerationsensing catheter near the mitral annulus may measure changes in LVfunction due to pacing. Both techniques may be used to optimize CRT LVlead implantation. The mapping system may also be used to determineoptimal RV pacing sites which may mitigate the need for placing an LVCRT lead.

Signals related to LV function include: earlier onset of motion relativeto the QRS; the interval time length of the LV cycle includingisovolumic contraction and relaxation, ejection, and filling; degree ofmitral regurgitation; peaks of isovolumic contraction and relaxation;and the myocardial performance index. One or more sensors or one or morefilters or both may be used to measure displacement or vibrational LVmotion and the LV cycle phases, as well as valvular pathology.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show graphs depicting various parameters of the cardiacpumping and ECG cycle.

FIG. 2 shows a drawing of an acceleration sensor mounted to a coronarystent.

FIG. 3 shows placement during use of the sensor and stent of FIG. 2.

FIG. 4 shows an alternative configuration of the sensor and stent, inwhich the same are conductively coupled to an IAD.

FIG. 5 shows a schematic of a system including a batteryless wirelessacceleration sensor, an antenna wand, and a data acquisition andprocessing system.

FIG. 6 shows an LV lead design to enhance flexibility between thesensors that detect myocardial strain or displacement.

FIG. 7 shows an alternate coiled LV lead design with enhancedflexibility.

FIG. 8 shows an IAD device for long-term monitoring of LV mechanicalperformance.

FIG. 9 shows an IAD integrated into an LV CRT pacing lead.

FIG. 10 shows an implantable LV lead with a sensor wire disposed suchthat it may be easily positioned at the mitral annulus edge.

FIG. 11 shows a cross-sectional view of the lead of FIG. 10.

FIG. 12 shows the lead of FIG. 10 in a bent position, showing inparticular the extension of the sensor.

FIG. 13 shows an implantable LV lead with a sensor disposed on theoutside of the LV lead.

FIG. 14 shows the lead of FIG. 13 when positioned partially in thecoronary sinus.

FIG. 15 shows a CRT acceleration sensing and control system.

FIG. 16 shows a flowchart of a data processing algorithm.

FIG. 17 shows a graph of velocity measured at the posterior-lateral edgeof the mitral annulus.

FIG. 18 shows a representation of long-term monitoring and therapyoptimization.

FIG. 19 shows the orientation of systolic and diastolic displacement aswell as measurement of the displacement length.

FIG. 20(A)-(C) show an assessment of LV size for acute response to CRTand long-term monitoring.

FIG. 21 shows positioning of a catheter employing multiple sensor pairsin the LV vein.

FIG. 22 shows a graph indicating location of a mapping catheter as wellas sensors in the LV.

FIG. 23 shows differing shortening or displacement patterns in variousregions of the heart.

FIG. 24 shows a method for mapping the LV for CRT LV lead placement.

FIG. 25 shows myocardial motion mapping, display output, and targetpacing identification.

FIG. 26 shows optimization of the pacing capture threshold.

FIG. 27 shows a multi-sensor multi-electrode mtion mapping cathetersystem.

FIG. 28 shows a more detailed view of the system of FIG. 27.

FIG. 29 shows acceleration signals used to identify regions of latedeformation and for assessing various other variables related toperformance such as MPI, IVC time interval, peak IVC height, etc.

FIG. 30 shows an alternative mapping strategy involving multiplecatheter repositionings.

FIG. 31 shows a roving pacing guidewire device and acceleration sensingcatheter for target pacing region identification as well as forcharacterizing the changes in LV function due to pacing.

FIG. 32 shows a guide catheter that may be used with the system of FIG.31.

FIG. 33 shows a system that may employ the guide wire of FIG. 31 or theguide catheter of FIG. 32.

FIGS. 35-38 show a system for identification of a target pacing regionand for optimizing and characterizing the pacing response.

FIGS. 39, 40A and 40B show a guide catheter acceleration sensor fordetermining valve closure with an LV lead acceleration sensor fordetermining myocardial motion via differential frequency processing.

FIGS. 41-44 show a mapping system for optimizing and identifying targetpacing regions.

FIGS. 45-46 shows a system for wire attachment to a sensor chip whichmay be employed in the construction of a sensing catheter.

FIG. 47 shows a circuit diagram that may be employed in embodiments ofthe invention.

FIG. 48 shows a printed circuit board layout that may be employed inembodiments of the invention.

DETAILED DESCRIPTION

Acceleration sensors are well-suited for measuring both vibration anddisplacement motions. They can be oriented along an appropriate axis tomaximize the motion signal and to accurately measure the displacement.An acceleration sensor placed in or on the heart can measure vibrationalor displacement components of heart motion, or both thereby allowing thecharacterization of pumping function and various pathologies.

The sensor may be based on MEMs principles, which allows forminiaturization and low power consumption. The design and fabrication ofcapacitance MEMs-based accelerometers are known to those skilled in theart. MEMs-based accelerometers are typically fabricated from silicon orsemiconductor substrates. In one illustrative system, the sensor isfabricated from a radiation-resistant semiconductor as the sensor willbe implanted in many cases under fluoroscopic guidance. The generaldesign of the accelerometer measures capacitance changes due to themovement of a proof mass beam with a side arm interdigitated between twocapacitor plates. As the proof mass beam and side arm move withacceleration or vibration, the capacitance changes and this signal canbe output as a measure of motion. These accelerometers are fabricatedfrom silicon substrates which allows for single-chip fabrication of thesensor with the necessary signal processing circuitry. This single-chipdesign increases the device's sensitivity as extremely small changes incapacitance can be measured. MEMs-based acceleration sensors asdescribed above can measure milli- or even micro-Gs (IG equals 9.8meters/sec²) which is suitable for myocardial acceleration measurementswhich may typically measure between 50 and 500 milli-Gs or higher.

Other acceleration sensor designs could also be utilized and are knownto those skilled in the art. For example, a thermal acceleration sensorcould also be employed in which the proof mass is a gas. Also, while amulti-axis (2 or 3 axes) sensor may be most useful, single axis sensorscould also be used and oriented appropriately to detect different axesof motion. It should also be noted that a pressure sensor can sensemotion and could be used in place of an acceleration sensor in certainsystems when determining the onset of motion relative to referencepoints such as the QRS or isovolumic contraction of mitral valveclosure.

Both the vibrational and displacement LV motion can provide usefulinformation for diagnosis of CRT candidates and optimization of CRTtherapy, as is described below. The sensors may be tuned to sensehigh-frequency, low-amplitude myocardial vibration, or low-frequency,high-amplitude displacement motion. Alternatively, the signal-processingfilters could eliminate or reduce frequency bands that are lower orhigher. For the purposes of this specification, high frequency signalsare those greater than about 150 Hz and are related to vibrationalmotion and correspond to valvular pathologies such as mitralregurgitation; intermediate frequencies range between about 20 and 150Hz can be used to sense vibrational motion and low-amplitudedisplacement motion related to isovolumic contraction or relaxation andvalve closure (e.g., aortic and mitral); low-frequency signals are thosewith frequencies less than about 10 Hz or 20 Hz and are used to detecthigh-amplitude displacement, both lengthening and shortening, related toejection and filling.

The frequency associated with the peak amplitude of valve closure isapproximately 40-60 Hz. Thus, when sensing in the mid-frequency range,and to sense valve closure events, a narrower band may be used in thisrange than the typical mid-frequency range. This signal is closelyrelated to isovolumic contraction and relaxation. Because many cardiacevents such as isovolumic contraction and mitral valve closure, or LVshortening and mitral regurgitation, or LV lengthening and mitral valveopening, occur simultaneously, two or more sensors or two or morefilters may be required to characterize these different cardiac signals.For the purposes of this specification, references made to the LVmotion, LV cycle phases (e.g., isovolumic contraction or relaxation),and valvular phenomenon (e.g., aortic, pulmonic, or mitral closure ormitral regurgitation), should be assumed to be sensed with one or moresensors, in the appropriate axis, at the appropriate frequency. Whilethis specification focuses on using valve closure events to providereference points for characterizing target pacing regions and CRToptimization, valve opening could also be used.

Sensors can be oriented in the devices described below to optimallydetect the desired LV motion. In one embodiment, a uniaxial sensor isoriented anatomically longitudinally (heart base to apex) to sensedisplacement of the LV. In addition, this sensor could detectvibrational motion through appropriate filtering. Alternatively, twouniaxial sensors oriented longitudinally and radially, i.e., toward theventricular chamber, or three uniaxial sensor oriented longitudinally,radially, and coronally may be used. A single triaxial sensor couldmeasure all these components. In another embodiment, two dual-axissensors are oriented perpendicularly to each other in the catheter orLV-lead device. Three axes may be used for LV motion sensing withfiltering used to detect motion at the appropriate frequency. The fourthaxis may be used as to detect valvular events such as closure or highfrequency pathologies such as mitral regurgitation. In still anotherembodiment, three dual-axis sensors may be oriented perpendicularly toeach other with the three axes used to detect displacement motion andthree axes used to detect mid- and high-frequency vibrations related toisovolumic contraction or relaxation and valvular pathology such asmitral regurgitation.

Implantable RF-Based Acceleration Sensor Devices

In one implantable embodiment, the MEMs-based sensor as described abovealso incorporates circuitry for electromagnetic (e.g., RF) inductivecoupling to create an RF sensor, as shown in FIGS. 2-5.

FIG. 2 shows the placement of a RF MEMS sensor 108 positioned on acoronary stent 112. A second sensor 108′ may be employed at a fixeddistance from sensor 108 for measurement of strain rate. An inductivecoil 114 can further be integrated into the stent 112. A third or moresensors 108″ may also be employed. This stent may be expanded in knownfashion, employing a balloon. Referring to FIG. 3, the stent and sensormay be disposed at a lateral edge 156 of the mitral annulus 148 forwireless long-term monitoring of LV 146 function.

In an alternative embodiment, shown in FIG. 4, the stent and sensor maybe conductively coupled to an IAD 154, having a battery, signalprocessing capability, and data transmission circuitry and capability.

In more detail, FIG. 5 shows a schematic diagram of a batterylesswireless acceleration sensor mounted to, e.g., a coronary stent, and acorresponding data acquisition and processing system. Referring to FIG.3, an RF MEMs acceleration sensor 108, in an optional single chipdesign, is shown coupled via an RF transmission scheme 120 to a receiversystem 114 which is in turn coupled to a data processing system 110. TheRF transmission scheme 120 may be employed both for inductive poweringand also for data transmission.

The MEMs acceleration sensor 108 includes an RF inductive coil 116 whichmay surround RF circuitry 118. RF circuitry 118 is coupled to signalprocessing circuitry 122. In another part of the chip, the capacitiveMEMS accelerometer 124 is resident. As further indicated in the figure,a microprocessor, as an ASIC or otherwise, may be integrated onto thechip as well, along with optional data storage 128. Additional detailsof the MEMs acceleration sensor 108 design are given below.

The receiver system 114 includes a wand 132 which encloses an antenna134 via which data and power are transmitted. An amplifier 136, such asa MMIC amplifier, may be employed to precondition the signal prior totransmission.

The data processing system 110 generally includes a microprocessor 138,a data output and display subsystem 142, and a data storage area 144.

A main component of the RF circuitry is the inductive coil which is usedfor data transmission and/or inductive powering. Alternatively, separatecoils could be used for inductive coupling and data transmission. Arepresentative silicon-etched inductive coil for powering capacitiveMEMs sensors is disclosed in U.S. Pat. No. 6,667,725. The RF circuitry,including the inductive coil, may be incorporated into the same sensorchip. Alternatively this circuitry and coil may be fabricated separatelyand conductively linked to the sensor. For example, a planar RF antennafor inductive powering and data transmission may be fabricated on aflexible polymer substrate (e.g., polyimide) by winding or etching. Theantenna may be planar. The sensor can be soldered to the flexibleantenna circuit at bonding pad areas. The flexible polymer may then bewrapped around a vascular stent or incorporated into other cardiacdevices and implanted into the body. In another embodiment a flat planarcoil on a polyimide substrate is created with a long thin section. Theplanar coil can reside subcutaneously and the long thin section canreside transvenously within the body or within a device such as an LVpacing lead.

In addition, non-volatile memory may be used for storage of capturedacceleration data. Similarly, this memory may be integrated into thesame sensor chip, but may also reside as a separate chip and or in aseparate location with appropriate connections. Lastly, amicrocontroller or an application-specific integrated circuit (ASIC) maybe incorporated into a sensor chip design or the same may reside on aseparate chip and in a separate location. It should be noted that alldevice descriptions below that are based on RF coupling could bereplaced with conductive element coupling for data transmission andpower supply from a battery.

The RF accelerometer sensor can be hermetically sealed and packaged in abiocompatible housing to form a rugged sensor device for implantationinto the body or cardiovascular system. Appropriate packaging may alsoreduce damage due to exposure to fluoroscopic radiation. Appropriatepackaging would also not interfere with RF coupling. The device wouldhave appropriate mechanisms for attachment to the body or cardiovascularsystem, including: tines, helical screws, suture pads, retention struts,and structures, such as porous titanium, to allow tissue ingrowth. Thereare various form factors the packaged accelerometer sensor device mayhave to facilitate implantation and various strategies for affixing thesensor device to the body.

An exemplary use of an RF sensor device is in cardiac surgery. Cardiacsurgery and transplant patients can have severe myocardial dysfunction.An RF sensor could be affixed to the epicardial surface of the left orright ventricle. In this embodiment, the packaged sensor device may becircular and 2 cm or less in diameter and less than 5 mm thick. Thedevice's epicardial surface may be flat and may have a helical screw forfixation into the myocardial tissue. Various polymeric materials maybeincorporated into the sensor epicardial surface to promote attachment tothe myocardium. The upper device surface is curvilinear to conform tothe chest wall. One or more sensors could be used to detect LV motionand related LV cycle phases, valve closure, and valve pathologies suchas mitral regurgitation. Again, conductive elements and a battery supplycould replace the RF components.

In another embodiment, an RF MEMs accelerometer sensor is incorporatedinto a coronary stent that is implanted in the LV arteries. The stentmay also be implanted in the lateral coronary sinus or great cardiacvein or other LV veins near or proximate to the lateral edge of themitral valve annulus. This is akin to implanting a sensor directly ontothe epicardium and hence acceleration sensing of LV motion and the LVcycle phases can be measured. If two or more sensors are used separatedby a known distance, strain and strain rate can be measured. The sensoror sensors could also be used to sense valve pathologies such as mitralregurgitation. Design and implantation of stents are known to thoseskilled in the art. The transceiver coil could be integrated into thestent body, or the stent body of a coiled stent design could serve asthe transceiver, as shown in FIGS. 2 and 3. In still another embodiment,RF acceleration sensors are incorporated into a CRT or CCM pacing leadand preferably the LV lead. In this way, the sensor monitoring may occurindependently of the CRT system via RF inductive powering and datatransmission. RF acceleration sensors incorporated into a CRT lead orCCM lead could measure LV motion and characterize LV function, includingvalve pathologies such as mitral regurgitation, as described below.Additionally, RF MEMs sensors may be incorporated into guide cathetersor guidewires for the same purpose.

RF sensor monitoring and data transfer could occur via an antenna deviceconnected to a microprocessor which is worn by the patient or held nearthe sensor (e.g., over the chest). An appropriate antenna device wouldhave a large enough antenna to inductively couple with the sensor. Inone illustrative system, the antenna device may couple with the sensorat a distance of 5 to 15 cm and up to 15 feet. An exemplary antennadevice is discussed in “RF telemetry system for an implantable bio-MEMssensor”, Rainee Simons, et al., NASA Glen Technical Reports, June 2004,NASA TM-2004-212899. As discussed in this paper, an MMIC amplifierconnected to the antenna can allow for a reduction in the size of thesensor coil and the reader antenna.

The antenna would transfer the sensor data to a microprocessor orcomputing device that applies processing algorithms to the data anddisplay the data to the physician for therapy monitoring. Themicroprocessor computing device and reader may be integrated into onedevice. Various signal processing functions may be carried out by themicroprocessor such as filtering different band widths for differentsensors to differentiate vibrational motion signals indicative of valveclosure or mitral regurgitation from lower-frequency displacement motionrelated to LV ejection or filling. Because patients may have variousvalve anomalies, such as mitral regurgitation or aortic stenosis, themotion related to isovolumic contraction and relaxation may beespecially monitored and may be indicative of valve closure events dueto the short time period (about 10-30 milliseconds) between isovolumiccontraction or relaxation and valve closure. Signals may be timed fordetection after onset of the QRS, an endocardial electrogram, or otherelectrical signals. For example, sensing isovolumic contraction mayoccur immediately after sensing of the QRS for an interval of 50-150 ms,i.e., to allow particular attention to be given to this period. Inaddition, the microprocessor could carry out various statisticalmanipulations to monitor long-term trends. It should be noted that themicroprocessor could also be located in an implantable deviceconductively coupled to the sensors.

Data transfer could be conducted by the physician periodically.Alternatively, the antenna device could be connected to the patient'shome computer and transferred data could be sent to a physician ormonitoring center over a network. An RF sensor-reading antennaintegrated into or connected to a cellular phone would allow data to bewirelessly transmitted to a physician or monitoring center. Similarly ahand-held computing device with wireless communications could transfersensor data wirelessly to a physician or monitoring center.

In another embodiment, at least one RF sensor, and even two or more, areincorporated into an endovascular catheter with or without a guidewirethrough lumen that can be implanted into the blood vessels of the body.In this illustrative system, at least one sensor is capable of sensingvalve closure, isovolumic contraction or relaxation phases, or mitralregurgitation either by sensor tuning or filtering. This sensor catheteris placed via transvascular methods form the subclavian vein, internaljugular, or cephalic vein into the coronary sinus, or its tributaries,including the left ventricle drainage veins. The proximal portion of thecatheter has a means for implantation and anchoring in the subcutaneoustissue.

Methods for inserting catheters into the coronary sinus and LV veins arewell-known to those skilled in the art. In general, insertion occursover a guidewire after accessing the coronary sinus ostium with a guidecatheter. This placement is done under fluoroscopic visualization so thesensors are constructed to withstand the radiation exposure or areotherwise protected in a capsule that does not interfere with RFcoupling. The catheter is flexible, may or may not be braided, and ismade of a biocompatible polymer such as silicone or PBAX. The sensorcatheter could have various features to facilitate placement andanchoring including fixed angles, a guidewire lumen, tines, and tipdeflectability or steerability. In addition, the catheter may have anocclusion balloon and contrast injection lumen and port for acquiring anLV venogram. Alternatively the venogram features are incorporated intothe guide catheter. Preferably, one sensor is located at theposterio-lateral or lateral edge of the mitral annulus. Additionalsensors may be located on the catheter separated by known fixeddistances (e.g. 5-10 mm) to provide strain and strain rate data. Theabove catheter allows long-term monitoring of myocardial mechanicalactivity and the LV cycle phases via wireless sensor powering and datatransmission, thereby minimizing device complexity.

Preferably the region of the catheter where the sensors are located issuitably flexible to move with the displacement motion of the heart.Referring to FIG. 4, if two sensors are employed to measure strain orstrain rate, the region between these two sensors should be suitablyflexible to ensure that the two sensors move relative to each otherduring LV displacement. The sensors may, e.g., move radially andlongitudinally relative to each other. The flexibility may be achievedby fabricating the region of the catheter where the sensors are locatedwith a metallic or polymeric helical coil. Alternatively, a thin-walledpolymeric catheter tubing could be employed. It may also important thatthe sensors lay adjacent to the myocardium as closely as possible or areprevented from moving within the vessel in a direction counter to thecontracting or relaxing myocardium. This may be accomplished byweighting the bottom portion of the catheter where the sensors arelocated such that they lie flat on the myocardium.

For example, referring to FIG. 6, a system is shown including a catheterhaving a coiled sensor segment or LV lead design which enhancesflexibility between the sensors for detecting myocardial strain ordisplacement. A catheter body 158 has a distal end 162 and adjacent todistal end 162 is sensor segment 164. A guidewire lumen 166 mayaccommodate a guidewire 168 for effective placement of the distal end162 of the catheter. The sensor segment 164 includes a metallic orpolymeric coil 178. A displacement sensor 172 may be mounted to the coil178, along with a sensor 174 to detect valve closure or isovolumicphases or mitral regurgitation. One or more electrodes 176 may also beprovided for sensing cardiac electrograms and delivering ablative RFenergy if required.

Alternatively, a structure can be used to constrain the sensors orsensor region of the catheter in the blood vessel, as shown in FIG. 7.This may be accomplished with a flexible wire cage that extends aroundthe sensors or sensor region of the catheter at a diameter approximatingor greater than the vessel diameter. An inflatable balloon or expandingdeployable structure could also be used to constrain the sensors orsensor region of the catheter in the vessel. Lastly, angling or coilingmay be employed of the region of the catheter with the sensors such thatthe bend helps constrain the sensor to the epicardium.

In particular, referring to FIG. 7, a system is shown in which a coiledsensor or LV lead design is disposed at the distal end of a catheter,the coiling allowing enhanced flexibility. A catheter body 182 has asensor segment 184 at the distal end 202 thereof A displacement-sensingsensor 188 is provided along with a sensor 186 which may measure valveclosure, isovolumic phases, or mitral regurgitation. Coils 192, 194, and196 provide enhanced flexibility for the sensor segment 184. It shouldbe noted that the actual number of coils and sensors may vary dependingon the design and requirements of the catheter. Coils 192, 194, and 196may have a polymeric or metallic construction. Sensor 186 may besurrounded by a wire cage 206 which may be employed for constraining thesensor at a predetermined location in a vessel. Wire cage 204 may servea similar purpose for sensor 188. The wire cages 206 and 204 furtherassist in preventing movement of the sensors during contraction.

Implantable Non RF-Powered Acceleration Sensor Devices

In an alternative illustrative embodiment, and referring to FIG. 8, anIAD (is fabricated by incorporation of one or more non-RF MEMsacceleration sensors into an LV venous catheter, as previouslydescribed. In this system, long-term monitoring of LV mechanicalperformance can be performed. Acceleration related to both LV vibrationand displacement, and valve pathologies such as mitral regurgitation,are measured by sensing at the appropriate frequency with the one ormore sensors and employing filtering and signal processing.

In particular, FIG. 8 shows a heart 200 and subclavian vein 216. Alsoshown is the left atrium 218, the right atrium 222, the right ventricle224, and the left ventricle 226. The catheter 210 may enter the heartthrough the subclavian vein 216, and extend through the coronary sinusostium 38 into the coronary sinus 242 adjacent to which is the mitralannulus 244. After passing partway through the coronary sinus, up to thecardiac vein 248, the catheter may extend into the LV vein 246.

The catheter 210 includes, near a first end 228, one or more sensors 208and 212. For appropriate sensing, the sensors may be separated by anapproximate pre-determined distance, e.g., 10 mm. One sensor may resideat the posterior-lateral edge 214 of the mitral annulus. The sensors maybe conductively connected via the catheter 210, at a second end 232, toa subcutaneously-implantable data acquisition and processing device 234,which contains a battery supply, RF telemetry circuitry, amicroprocessor, and data storage. The implantable data acquisition andprocessing device may be housed in a hermetically-sealed titanium shell.The processing unit 234 may connect to the catheter 210 via a proximalcatheter connector 236. The sensors are encapsulated in a structure thatprotects them from fluoroscopic radiation damage; however, because thesensors in this embodiment are not directly RF-coupled, concerns aboutinterfering with this coupling are eliminated. Insulated, multifillar,coiled wires 252, only a portion of which are shown in FIG. 8 forclarity, conductively connect the sensors to the proximal catheterconnector 236. The connector attaches to the implantable dataacquisition and microprocessor device 234, which powers the sensors,captures the sensor data, processes the data, and stores the data. Themicroprocessor controls the data sampling period and data samplingintervals. Captured acceleration data can be subjected to various dataprocessing algorithms as are described below. This processed data can bestored in memory for later RF telemetry data transfer.

The battery in this embodiment may be rechargeable or typical ofimplantable battery sources. A typical implantable battery cell designis lithium silver vanadium oxide. Lithium carbon monoflouride may bealso be used and has certain advantages due to its low weight.

Data storage may include readable and writable memory. A constant powerinput from the battery can allow volatile random access memory to beused for data storage and control functions. However, non-volatile datastorage such as eeprom or flash may also be used. A combination ofvolatile and non-volatile memory storage may be used. Flash memory isnon-volatile, compact and operates in the voltage range of implantabledevice batteries. Access to the data is rapid and megabyte storagecapacity is available in a small size. Data may be stored on afirst-in-first-out basis if memory becomes full prior to RF telemetrydata transfer.

IAD acceleration data acquisition occurs over a sampling period that maybe continuous or may be only a short period such as several seconds toup to 30 seconds or even several minutes. Data acquisition may occur atvarious sampling intervals such as from 8 to 1,440 times each day.Sensor data is sampled at rates sufficiently high to provide usefulinformation for diagnosis and monitoring of CRT patients, target pacingregions, and heart failure (or cardiomyopathy) patients, and preferablyat rates of 100 per second to 1000 per second. Sample rate, sample time,and interval periods are in part dependent on data storage capacity.Data captured and stored can be transferred by telemetry to a computingdevice either daily by the patient or weekly to monthly or longer by thephysician. Data storage may be sufficient to allow at least one day ofdata storage and up to six months of data storage at the optimal datasampling rate, time, and interval to provide the physician with usefulinformation.

In another illustrative system the IAD described above is integratedwith the proximal portion of a cardiac pacing lead, and preferably an LVCRT pacing lead, as shown in FIG. 9. At least one and possibly twosensors or more, shown as sensors 254-262, are incorporated into the LVpacing lead to measure LV motion and characterize LV function. Thecatheter may have an endovascular portion 270, and a subcutaneousportion 280, with a subcutaneous anchoring device 272 to anchor theadjacent portion of the catheter to the chest wall.

If strain or strain rate data is to be measured, two or more sensors maybe incorporated at a known distance from each other, e.g., 5, 10, or 15mm. One or more sensors are positioned on the lead as in the aboveembodiments with least one sensor residing at or near theposterior-lateral or lateral edge of the mitral valve annulus. Theregion of the lead between and around the sensors is made suitablyflexible as previously described to ensure measurement of LVdisplacement and strain or strain rate. Sensing is carried out atdifferent frequencies or with one or more sensors, or both, to measureboth displacement and vibration to characterize the LV cycle phases andfunction, and pathologies such as mitral regurgitation. ThisIAD-integrated cardiac lead design allows cardiac mechanical monitoringindependent of the CRT or CCM IPG. In this pacing lead embodiment, animplantable data acquisition and processor component 278 may be made assmall as possible. Thus the battery cell used may be ultra miniature andmay be rechargeable. Exemplary batteries are available from Quallion,Inc., of Sylmar, Calif., some of which have a 2.9 mm outer diametercylindrical implantable battery (2.7-4.0 V, 3 mAmp-hours). A compact,non-volatile memory such as flash memory may be used in this system forprocessed data storage. Data processing algorithms may be performedafter RF telemetry data transfer. The IAD RF telemetry may occur at afrequency that does not interfere with a CRT device 284. In addition tothe battery power, data storage, and RF telemetry components, theimplantable accelerometer data processor 278 may include amicroprocessor, and may connect to the catheter via connector 282 at adistal end of Y-connector portion 290.

The catheter may be disposed using guide wire 274 having distal tip 292adjacent tine 298, the guide wire being enclosed within a guidewirelumen (not shown).

Data and signals from the sensors and the data acquisition andprocessing component 278 are sent to the CRT device 284 via connector276. The CRT device 284 may also receive signals from RA lead 286 and RVlead 288.

The design of LV pacing leads is known to those skilled in the art. Ingeneral, the LV CRT lead and fixation is similar to currently deployedleads with the exception of the requirement of accommodating theaccelerometer-based sensors. The lead may be unipolar or bipolar. Theconductive wires for the electrode may be coiled, mutifillar, andsheathed in a polymer such as silicone or polyurethane. A connector 276at the proximal end 277 allows connection to the IPG and may beuniversal according to the IS-1 standard. A set of pacing electrodes264-268 and 296 can be variously fabricated as a blunt-nosed tip (296),ring (264-268), or coiled. Non-corrosive alloys and metals can be usedin the electrodes/lead such as platinum iridium or titanium iridiumoxide or nickel cobalt or others such as are known in the art. The leadmay elute a steroid drug via a drug elution component 294 to minimizeinflammation at the electrode site location to keep capture thresholdslower. The lead could also have an ePTFE coating at the electrode tominimize fibrosis.

In another illustrative LV lead implantable system, a sensor 302 isincorporated into a sensor wire 304 that integrates with an implantableLV lead 300 (See FIGS. 10-14). This design allows the pacing lead to bepositioned in the target pacing region and LV vein and the sensor can bepositioned along the lateral or posterior edge of the mitral annulus.The sensor wire can also serve as a guidewire for the LV lead 300. Thesensor 302 is attached to the sensor wire 304 via a stalk 306. Theelectrical conductors 308 of the sensor 302 run through the stalk 306and down the length of the sensor wire 304. At the proximal end 310 ofthe sensor wire 304 is a connector 312 for linking the sensor 302 to anIAD 314. Even more proximal of end 310 may be a connector 342 toconnecting the LV lead to a CRT device 344.

The sensor wire is integrated into the LV lead via a side wire lumen 316along the length of the LV lead 300. The side wire lumen 316 is split toallow the sensor to be shuttled along the surface of the lead body 300.The sensor wire 304 may reside in the side wire lumen 316 and the sensorstalk 306 may reside along the split in the lumen 316. Thus theacceleration sensor 302 can be shuttled to the desired location at themitral annulus 322 (see FIG. 14), such as near to the lateral border 326of the mitral annulus 322, while the pacing lead 324 can go to thetarget pacing region, e.g., region 330. If the pacing lead 324 makes abend to cannulate and LV branch that feeds into the coronary sinus, thesensor wire 304 can continue straight within the coronary sinus 326 orgreat cardiac vein to the desired location. In other words, the sensorcan be placed in a desirable location for measuring LV function whilethe pacing lead is disposed in the proper location for pacing of theventricle.

Also shown in FIG. 10 is a central guide wire lumen 318 (which emergesfrom opening 336) that may be employed to position the LV lead 300, aswell as components of the pacing lead 324, such as ring electrode 332,optional acceleration sensor 334, and microporous tip electrode 338.

In use, as the LV lead 300 bends to enter the posterior to lateral LVvein 342, the sensor wire 304 and sensor 302 bend out of the side lumen316 due to the stiffness of the sensor wire 304. In this way, while theLV lead 300 goes into the LV vein 342, the sensor 302 continues on to aposition near the mitral annulus or the lateral border thereof.

In another illustrative system, as shown in FIG. 15, the IAD isintegrated with the CRT or CCM IPG device, here shown as device 350 Inthis CRT acceleration sensing and control system, sensor data is used tocontrol the output of pacing signals to electrodes in regions of latecontraction and deformation.

As before, acceleration sensors 352-358 are integrated into the LVpacing lead 360. Circuitry and control of sensor data acquisition andprocessing may be integrated with the electronics of the CRT.Algorithm-processed acceleration data, described below, can be used tocontrol and optimize the CRT such as via the atrioventricular interval,the interventricular interval, and may further be used to optimize theLV pacing site. Motion sensing may be used to dynamically change thepacing at multiple LV electrodes to continuously optimize the LV pacingover time. Cardiac events such as valve closure or isovolumic phasescould control the timing, similar to a cardiac electrogram. At least onesensor may be designed to detect valve closure or isovolumic contractionand relaxation and may be positioned in the vessel to do so. Such adevice that senses mechanical cardiac activity, e.g., valvular events,isovolumic contraction phases, and deformation, may be more optimal thancontrolling pacing signals with a sensed cardiac electrogram sincecardiomyopathy causes mechanical dyssynchrony. Because some CRTs havedefibrillation capability, the sensors and their attendant circuitry mayhave to withstand the energy delivered during a defibrillation event.This device may be capable of standard CRT functions, includingmulti-chamber EGM sensing, pacing, and trigger or inhibition control.Event sensing and storage would also be typical. Antitachyarrhythmia andbradyarrhythmia control of the atria and ventricles as is currentlyavailable may also be present and may include overdrive pacing,cardioversion and defibrillation. The device also allows periodicassessment of electrode capture threshold and adjustments to thisthreshold. This preserves battery life and ensures optimal myocardialactivation and therapy. Hence myocardial deformation or strain rate maybe monitored and pacing signals directed to the electrode where latedeformation is occurring. Consequently, this type of CRT system may havean LV lead with multiple electrodes and acceleration sensors.

In more detail, device 350 may be connected to various leads viaconnector 392. The leads may be RA lead 370, RV lead 380, and LV lead360. The RA lead 370 and the RV lead 380 may have optional accelerationsensors 346 and 348, as well as electrodes 362 and 364, and helicalfixation points 378 and 382. Besides the acceleration sensors alreadynoted on LV lead 360, a number of electrodes 366-374 may also bedisposed. A guide wire lumen 384 may be disposed for use with a guidewire to aid is positioning the lead. The distal tip of the lead mayinclude a tine 376 to help stabilize the lead in the vein. An optionalballoon occluder 386 may be employed for venogram acquisition, with acontrast injection port 388 adjacent, but distal, thereto. The remainderof the catheter system is as has been already described.

Signal Processing, Data Analysis, and Monitoring

In one illustrative system, the LV motion signals and data analysis areproduced from a sensor along the mitral valve annulus. Mitral annularvelocities have been shown to provide an accurate assessment of globalleft systolic and diastolic function. Mitral annular motion may also bebest to measure displacement of the LV. Thus, this displacement motionmay be subjected to a mathematical integration algorithm, as shown inFIG. 16, to yield velocity and distance.

In particular, the first step is to acquire acceleration data (step394). Following this initial step, the data may be averaged over apredetermined sample period (step 396). The acceleration data may thenbe integrated to obtain the velocity (step 398).

A velocity curve may then be output to indicate systole and diastolicvelocities (step 402). From this an analysis of peaks over time may beoutput (step 404). Finally, a measurement may be taken of the onset ofdisplacement velocity versus the QRS peak (step 406).

If a second sensor acquires, or can be used to acquire, velocity data aswell (step 408), displacement and strain rate may be obtained. From thefirst and second sensor velocity data, the strain rate can be calculated(step 412), and a strain rate curve may be output (step 416). From thestrain rate and the velocity data, the data can be integrated to obtainthe ventricular displacement (step 414), from which a displacement curvemay be output (step 418). In general, LV motion signals may be processedin a manner best used for interpretation and therapy optimization. Thisincludes analyzing indices or variables of LV function such as: peaksand slopes of acceleration, velocity, and distance curves, intervaltimes of LV cycle phases, and analysis of pathological valve signals.Curves, such as a velocity curve of LV displacement, may be plotted withvelocity in millimeters or centimeters/sec as the ordinate and cardiaccycle time in milliseconds as the abscissa. The algorithm may alsoinvolve calculating strain rate by processing acceleration data from atleast two sensors separated by a known distance, e.g., 5 to 15 mmmillimeters apart. Vibrational motion signals, e.g., that related tomitral regurgitation, may be presented as an amplitude and duration or achange in the frequency.

3-axis sensing is utilized in some illustrative systems. A more accuratemeasurement of peak amplitude can be measured by calculating thecomposite acceleration vector of each axis (x, y, and z). This canaccount for the gravitational acceleration and its effects on sensortilting. The composite vector can be calculated by taking the squareroot of the sum of the x-axis measurement squared plus the y-axismeasurement squared plus the z-axis measurement squared. This peakamplitude calculation can be applied to both the vibrational motion andthe displacement motion. This may be particularly accurate during theimplantation of an LV lead for CRT therapy when the patient is lyingstill on a procedure table. Here the sensor measures the peak in the LVveins or coronary sinus.

Thus, LV acceleration signals are sampled at a designated rate for a settime period, which is the sample period. Sensor data from the sampleperiod can be averaged over several or more cardiac cycles to smooth outeffects related to respiration and patient motion. The averaged data canthen be used to produce a cardiac cycle acceleration curve whichincludes tissue acceleration, in, e.g., mm or cm/sec² versus cardiaccycle time, in milliseconds. This curve can then be mathematicallyintegrated to produce a tissue velocity curve, e.g., in mm-cm/sec vs.cardiac cycle time. A second integration can performed to produce adistance curve, with units of mm or cm. Point-by-point accelerationsensing and integration can also be performed with peak identification,integration, and presentation as an individual data point rather than acurve.

Strain and strain rate curves and data points may be generated fromvelocity curves or data points. Generally at least two sensors areneeded to measure strain rate. Velocity curves or data are generatedfrom the two sensors in at least one axis. Strain rate or strain ratecurves are created by integrating the difference in velocity data fromthe two sensors at the same point in the cardiac cycle and dividing thisdifference by the distance between the sensors ∫(v₁−v₂)/l . Since thedistance of the sensors along the length of the implanted catheter orpacing lead is fixed, the distance between sensors is known. The straincurve is generated by integrating the strain rate curve.

Referring to FIG. 17, the velocity of LV displacement from the mitralannulus, generally at the posterior-lateral edge thereof, produces peaksrepresentative of LV function during systole and diastole. Analysis ofthe peaks including: magnitude of the change, e.g., positive andnegative, peak slopes, peak/peak ratios, slope/slope ratios, peak/sloperatios, and peak integration, provides specific information on LVfunction related to contractility, afterload, volume status, preload,ventricular compliance, ejection fraction, and ventricular synchrony. Asabove, FIG. 17 and the like may represent a composite of all three axes,x, y, and z, of the acceleration sensor.

This information is useful for the physician for long term management ofthe cardiomyopathic patient. This curve 422 often has two peaks duringsystole (S1 424 and S2 426) and three peaks during diastole (isovolumicrelaxation 428, E 432, and A 434), though at times not all of the peaksare discernable. Trends in these peaks can provide useful information tothe physician. These trends may prompt changes in pharmacologic therapysuch as drug addition/elimination or dosage changes.

For example, referring to FIG. 18, which shows a representation oflong-term monitoring and therapy optimization, a patient is seen with abaseline level of maximum peak magnitude of the average of daily sampleintervals of S1 or S2 annular velocities (line 436, with a standarderror of mean (SEM) of daily average peak data 437 and 437′). Decline438 may be seen, which corresponds to a decline in contractility, e.g.,of the S1 peak. The decline may be defined in various ways, such as by aone or two SEM deviation from the baseline. A therapeutic interventionat 442 is shown, which is done to improve contractility. A new baselineis then evident at 444, with SEM bars at 446 and 446′.

These trends may also indicate when additional interventions arewarranted such as cardiac surgery, endovascular revascularization, orCRT. It may be noted that these peaks have been characterized withtissue Doppler imaging at the posterio-lateral edge of the mitral valveannulus in a single plane. An epicardial acceleration sensor in the sameregion, that is recording acceleration in 1, 2 or 3 axes, may produce asomewhat different velocity curve. However, it is believed that thecurve can be analyzed in a manner analogous or similar to that discussedbelow to provide useful information to the physician.

The S1 peak can be used to assess myocardial contractility with a higherpeak indicating improved contractility and a lower peak indicatingreduced contractility. A main goal of heart failure therapy is toimprove myocardial contractility. Contractility can be improved with CRTtherapy and pharmacologic therapy. The slope of this peak may providesimilar information.

The S2 peak can be used to assess afterload, which is a measure of theresistance the heart must pump against as it circulates blood to thebody. It is the goal of heart failure therapy to reduce afterload,primarily with the use of pharmacologic agents. Increases in the S2 peakrepresents increases in afterload, and decreases in the S2 peakrepresents reductions in afterload. Alternatively, integrating the areaunder the S2 peak may provide information on the afterload. The S2 peakalso correlates with ejection fraction and rate of pressure change(dP/dt).

The E and A peaks can be used to assess cardiac compliance and patientvolume status. In heart failure therapy, optimizing the patient's volumestatus and its effect on left heart pressure is important.Cardiomyopathy patients have a tendency to retain water and can becomevolume overloaded. When this occurs, the function of the heartdeteriorates and symptoms such as pulmonary congestion occur. Diureticdrugs such as Lasix are commonly used to reduce water retention.Monitoring of the E and A peaks and slopes, and integrating the areaunder the curve, can provide information on volume status. In addition,the relationship of the E and A peaks (E/A) is indicative of ventricularcompliance. Ventricular compliance can change with ischemic events andcan be reduced with long-term elevated afterload. Beta-blocker therapycan affect compliance in cardiomyopathy patients and therefore may bemonitored with the E and A peak data.

The A peak which represents atrial contraction can also be used tooptimize atrioventricular timing in a patient with CRT therapy. AVsynchrony optimizes preloading of the heart and improves pumpingperformance in part via the Frank Starling mechanism. Ideally,ventricular contraction occurs at the completion of atrial contraction,which produces optimal preloading of the ventricle. The end of atrialcontraction and ventricular filling can be determined at the point atwhich the ventricular velocity crosses the abscissa after the peak ofthe A wave (FIG. 11). Subsequently, ventricular pacing signals can betriggered at this point.

Other measures of LV function can also be obtained by analyzing the timeintervals of different phases of the cardiac cycle. Several timeinterval measures include the isovolumic contraction, ejection phase,isovolumic relaxation and LV filling time. Time intervals can beestimated from the acceleration, velocity, and distance data. The startof a time interval may be identified as an acceleration amplitude abovea certain threshold (e.g., +/−milli Gs) and the end of an interval maybe indicated by the dipping of the acceleration amplitude below athreshold value. Also, the number of zero crossings may also be used toestimate time intervals. A reduction in the isovolumic contraction orrelaxation time interval would be indicative of a favorable response.Increase in the ejection phase time interval, e.g., QRS to aortic orpulmonic valve closure, and the filling time interval, would also beindicative of a favorable response.

The myocardial performance index (MPI) is a measure of systolic anddiastolic function that is a good predictor and monitoring indicator forheart failure. The index is calculated as the isovolumic contractiontime plus the isovolumic relaxation time divided by the ejection phasetime (FIGS. 18 and 21). A reduction in the value of the MPI isindicative of better LV function. The MPI may be assessed using anacceleration sensor by measuring the intervals as described above. Inaddition it may be assessed by monitoring mitral valve opening andclosing from the coronary sinus or great cardiac vein and measuring theejection phase due to LV shortening. Thus the time interval duringsystole between mitral valve closure and mitral valve opening minus thetime interval of LV shortening divided by the time interval of LVshortening is indicative of the MPI.

Longitudinal displacement of the mitral annulus inferiorly duringsystole and superiorly during diastole is also a good measure of LVfunction. Thus a sensor in the coronary sinus or proximal the greatcardiac vein with at least one axis oriented longitudinally will measurethe acceleration of the annular region in the inferior and superiordirections. From this, velocity and distance can be calculated throughintegration. The peak acceleration, peak velocity, and distance traveledby the annular region during systole are indicative of performance withhigher values indicating better function. Similarly the velocity andpeak acceleration during diastole as well as the distance traveled is ameasure of LV performance with higher values indicating better function.The clockwise or counterclockwise rotation of the basal and annularregion can be measured in the coronary sinus with an acceleration sensororiented horizontally. Again, higher values of acceleration, velocity,and rotation are indicative of LV performance. Narrowing and wideninganteriorly/posterialy and medial/laterally of the mitral annulus is alsoindicative of LV function. An acceleration sensor oriented radially tothe heart in the coronary sinus or proximal the great cardiac vein couldassess this motion with higher values indicative of better function. A3-axis sensor could measure all axes of motion of the mitral annulus:longitudinal, radial, and rotational, for complete characterization ofLV function from the coronary sinus. This would be useful for long termmonitoring, identifying, and optimizing LV pacing regions during CRTlead placement as described below.

Referring to FIG. 19, in which displacement, in, e.g., cm or mm, isshown as the ordinate, low frequency (1 to 10 Hz or less than 20 Hz)acceleration sensing associated with LV displacement and its respectiveintegration of velocity and distance may appear as a semi-sinusoidalwave (curve 448) of positive and negative deflections with a frequencyas a function of the heart rate. The orientation of the sensor axesdetermines if longitudinal displacement is a positive deflection or anegative deflection. By convention, longitudinal shortening is usuallydisplayed as a negative or downward-moving deflection and lengthening asa positive or upward-moving deflection. If the orientation of the sensoris not known and cannot be determined easily, information recorded bythe sensor may not allow the physician to distinguish systolicshortening from diastolic lengthening. Orientation can be determined bysynchronizing the low frequency sensor data with the high frequency dataor the QRS (see curve 458 and points 454, which signify mid-frequency(20-150 Hz) valve closure signals. Isovolumic contraction and relaxationsignals occur with a similar mid-frequency.). Thus, the start of systoleand shortening can be determined as the deflection that occurs afterisovolumetric contraction, mitral valve closure, or alternatively theQRS. The double integration of the peak amplitude of the sensor dataafter mitral valve closure or isovolumic contraction or QRS isrepresentative of peak longitudinal shortening. The same rationale canbe applied to orienting longitudinal lengthening using isovolumicrelaxation or the aortic valve closure sensor data or the T-wave (seeFIG. 1B) as the reference point. Isovolumic contraction or relaxation ormitral or aortic valve closure can have distinctive vibrational signalsdetected by higher frequency sensing, allowing the same to bedistinguished. However, mitral valve closure can be determined bycomparing the sensor signal to the ECG, whereas the mitral valve signalwill be the first signal detected after the QRS. The microprocessor canbe programmed to display the shortening and lengthening according toconvention.

To accurately measure the length or magnitude of ventriculardeformation, peak velocities, or peak accelerations, during systole (oreven diastole) along the radial or longitudinal axes, a zero referencepoint is preferably ascertained. This can be seen in FIG. 19 as point456, for the zero point systolic deformation for length measurement,which also represents the peak diastolic length. A different peak 458represents the zero point diastolic displacement, which is also the peaksystolic shortening. As the sensor devices are maneuvered in the patientor as a patient moves, the tilt of the sensor with respect to gravity,i.e., the angle versus the gravity vector, will change. This sensoroutput due to the tilt signal must be accounted for or offset toaccurately measure peak amplitudes and distance of shortening. Formechanical mapping (see below), the magnitude of shortening, or peakvelocities or peak acceleration, could be assessed and regions that areactivated earlier and have a greater magnitude of shortening would beselected for long-term CRT pacing. Also, the optimal pacing capturethreshold could be determined by applying pacing signals of increasingstrength (millivolts). Monitoring the magnitude of the deformation andcorrelating this with the pacing signal strength optimizes the pacingthreshold (see FIG. 26. Further, the qualitative assessment oflengthening or shortening is facilitated by having a zero point.

Referring again to FIG. 19, valve closure or isovolumic contraction orrelaxation can provide the zero-offset reference point. Alternatively,the onset of the QRS can be used to determine the zero point. Hence,length of systolic shortening 460 is measured as the peak amplitude ofthe double integration of acceleration data sensed after isovolumiccontraction and/or mitral valve closure or QRS onset. Similarly, thelength of diastolic lengthening 450 is measured as the peak amplitude ofthe double integration of the acceleration data after isovolumicrelaxation and/or aortic valve closure, i.e., the diastolic zero point.The tilt reading, or tilt offset, of the sensor can also be accountedfor by using the QRS onset, mitral valve closure, or aortic valveclosure from the signals measured. Thus, the capacitive signal sensed bythe sensor at the above reference points can be subtracted out fromsubsequent signals being measured to detect LV lengthening andshortening. Accurate assessment of diastolic lengthening as noted aboveallows the physician to monitor the filling and the dilated state of theleft ventricle.

Trends of increasing diastolic lengthening are indicative of volumeoverload, while reduction in diastolic lengthening representsimprovements due to volume unloading. This data may be trended in animplantable device according to an embodiment of the current inventionand is useful in the mapping procedure to assess the effect of pacingthe target region which may then shows a reduction in peak diastoliclengthening due to improved pumping and volume unloading.

Referring to FIG. 20(A)-(C), assessment of LV size for acute response toCRT and long-term management is shown. As heart patients regain fluidthe LV can become enlarged. Benefits are seen as reduced LV volumes. Byhaving a sensor on the lateral wall, the relative movement as the LV isenlarged could be monitored. Sensors also allow the establishment of areference point.

FIG. 20(A)-(B) shows mitral annulus 462, LV wall 464, and cardiac vein466 in which is situated high frequence sensor 468 and low frequencysensor 472. FIG. 20(B) shows the position of the sensor on the heart atthe end of the filling phase (post isovolumic relaxation). If the heartimproves, the sensor moves inward to reflect the smaller size (FIG.20(A)). If the heart enlarges the sensor moves outward (FIG. 20(C)).Thus, used in this was, embodiments of the invention give a measure ofdiastolic filling or dilation.

Mitral regurgitation can be caused by LV dilation and functionaldecline, which worsens the symptoms of heart failure and is associatedwith faster deterioration of the heart. CRT can improve mitralregurgitation. Mitral regurgitation can cause higher frequency (>200 Hz)motion that can be sensed at the mitral valve annulus from the LVvasculature with the acceleration sensor. The amplitude of theacceleration signal and duration relative to the ejection phase may begood indices to measure for improvement. A reduction in amplitude andduration is indicative of improvement. A change in the frequency mayalso be indicative of improvement. The vibrational motion associatedwith isovolumic contraction may be indicative of the contractility ofthe heart. Increases in the peak of this signal may indicate bettercontractile function.

For trend monitoring (e.g., with an IAD), acceleration data is sampledat regular intervals during the day, termed the “interval period”, andthis data is averaged. Peak amplitudes can be plotted as the ordinatewith the monitored time interval (e.g., days, weeks, or months) as theabscissa (See FIG. 18). Data points may indicate the average amplitudeof the peaks from the interval samples. Statistical analysis of thesetrends can identify changes from baseline function that may warrant anintervention.

Disposable and Mapping Acceleration Sensor Devices

LV motion may be useful for identifying target pacing regions for CRT.

Target pacing regions may be identified by how late the region of the LVstarts shortening relative to a reference point such as onset of systoleor end of systole (See, e.g., FIGS. 21-24).

Referring to FIG. 21, a catheter 462, which may perform mapping, isshown within the posterior LV or lateral LV 464, and in particularwithin the LV vein 466. The catheter 462 includes a sensor pair 468, asensor pair 472, and a sensor pair 474. The catheter 462 also includeselectrodes 476. Area 470 indicates the segment of late displacement. Themitral annulus is shown at position 478.

FIG. 22 shows displacement curves which identify a late shorteningsegment in the posterior region. Pacing of this region causes earlierdisplacement and synchrony with other segments. The abscissa representtime in milliseconds. The ordinate represents ventricular displacement,but similar curves may be drawn representing velocity or strain rate.The measurement from sensor pair 468 is shown by curve 482; themeasurement from sensor pair 472 is shown by curve 484; and themeasurement from sensor pair 474 is shown by curve 486. An ECG is shownas curve 488, with representative QRS waveforms.

Along curve 482, feature 492 represents late shortening. Feature 494represents a pacing signal from one of electrodes 476, in particular anelectrode adjacent sensor pair 468. Feature 496 depicts earliershortening of the late segment and optimized ventricular synchrony.Along curve 486, the baseline is chosen as the sensor position at QRSonset, or the onset of isovolumic contraction, or the end of the A-wave.The negative deflection shown in feature 498 reflects the shortening ofthe LV.

Uncoordinated LV contraction due to delayed regional shortening reducesthe efficiency and effectiveness of blood pumping and hence delayedregions are targets for pacing. Myocardial shortening that occurs afteraortic valve closure, i.e., post-systolic, does not contribute to theejection of blood and may exacerbate pathologic conditions such asmitral regurgitation and hence these regions are also targets forpacing. Both longitudinal and radial shortening may be delayed. Lateonset shortening or post-systolic shortening may be best measured at lowfrequency acceleration signals related to displacement. The integrationof the acceleration signal to a velocity or distance may also smooth outthe signal and make it easier for the physician to interpret. Areference point for delayed systolic shortening and post-systolicshortening may be the QRS onset and T-wave, respectively.

FIG. 23, shows various shortenings or displacement patterns in variousregions that indicate dyssynchronous LV signals and probable respondersto CRT. Delayed onset shortenings and post-systolic shortenings aretarget pacing regions.

Curve 502 represents an ECG with the Q, RS, and T waveforms shown. Curve516, which is straight, shows sound waveforms of the MVC and AVC. Curve504 represents a post-mid-segment measurement. Curve 506 represents apost-basal measurement. Curve 508 represents a post-basal-lateralmeasurement. Curve 512 represents a basal-lateral measurement. Curve 514represents a mid-lateral measurement. Various features of these curveswill now be described. In all the curves, points 526 represent the zeropoint position of the sensor at either QRS onset, MVC, or AVC. Also inall curves, the target pacing region was the basal lateral, and theexample shows delayed onset shortening, early systolic lengthening, andpost-systolic shortening.

Referring to curve 504 in FIG. 23, features 516 represent a shorteningand lengthening dyssynchronous pattern. Features 518 show adysssynchronous contraction pattern. Referring to curve 506, which showsa delayed hypokinetic response, feature 522 reveals a delayed onsetmotion relative to the QRS or MVC. Feature 524 reveals a reduced peakdisplacement or shortening hypokinesis. Curve 508 shows an akinetic ordyskinetic response. Curve 526 shows a dyskinetic response withpost-systolic shortening. This curve also shows early systoliclengthening at feature 528, post-systolic shortening relative to AVC atfeature 532, and normalized displacement or shortening at feature 534following pacing spike 530. Curve 514 shows a normal heart rhythm withpeak shortening at feature 536.

Alternatively, vibrational components of the LV cycle may be used asreference points. Thus a reference point for delayed systolic shorteningwithin systole may be the vibrational motion associated with isovolumiccontraction or mitral valve closure. Similarly, vibrational motionassociated with isovolumic relaxation or aortic valve closure may serveas reference points for post-systolic shortening. These reference pointsoccur in the mid-frequency range (e.g., 20 Hz-150 Hz), while thedisplacement motion occurs at the low frequency range (e.g., <10 Hz).These signals can thus be separated out by appropriate filtering. Postsystolic shortening more than about 20-50 milliseconds or greater than20% of the total regional shortening after aortic valve closure could bea target pacing region. Other targets are dyskinetic regions that haveperiods of lengthening during early systole followed by shorteningdeformation, or akinetic regions that have lengthening throughoutsystole (FIG. 16).

LV motion, both regional and global, can be used to characterize indicesof LV function in response to pacing. Thus, identification of a regionof late or post-systolic shortening may be performed, and/or a pacingelectrode can be positioned in the region and paced at a threshold thatensures tissue capture.

FIG. 17 shows a mapping method, for the LV, for CRT LV lead placement. Afirst step is to place the guide catheter in the coronary sinus (step538). A next step is to insert the catheter with the acceleration sensorinto the guide catheter and into the coronary sinus (step 542). A nextstep, which is optional, is to measure the onset of displacement motion,e.g., velocity or distance, relative to the onset of systole, asdetermined via QRS or isovolumic contraction (step 544). Step 544 may beperformed by moving the catheter in the coronary sinus and great cardiacvein or tributary veins, e.g., in a septal to lateral manner. A nextstep is to insert the pacing guide wire through the guide wire lumen ofthe acceleration sensing catheter and then into the tributary veins ofthe coronary sinus and the great cardiac vein (step 546), e.g., thebasal, mid, and apical regions. A next step is to pace the region in thetributary vein (step 548). A next step is to measure the accelerationsignal characteristic of LV function, e.g., QRS to AVC; the myocardiaperformance index (MPI); or mitral regurgitation (step 552), for whichthe peak acceleration is at the isovolumic contraction. The final stepis to insert the LV lead over the guidewire to the target region, i.e.,the region with improved LV function (step 554).

Referring to FIGS. 25 and 33, which shows myocardial motion mapping,display output, and target pacing identification through a roving paceguidewire, changes or variables indicative of a favorable LV functionalresponse may be sensed at the low, mid, and high frequency ranges. Inthe figure, “MVR” refers to mitral valve regurgitation, “IVC” refers toisovolumic contraction, and “IVR” refers to isovolumic relaxation. Thetop curve is ECG 556, curve 558 shows the velocity or LV displacement,obtained by integrating the acceleration signal, curve 562 shows LVfunction, and curve 562 shows the sounds of mitral valve regurgitation.

ECG 556 shows the QRS and T waves along with a pacing spike 566 which isdelivered in the LV vein region. Examination of curve 558 shows adelayed onset motion 568 but a lessened delayed onset motion 572following the pacing spike. Curve 562 shows a value of ejection phase574, as measured by the time between the MVC or IVC and the AVC or IVR,and then a longer ejection phase 576. Here the MPI can be seen to beMPI=(a+b)/c. Finally, curve 564 shows a reduced MVR signal 578 ascompared to the pre-pacing MVR signal 582.

As shown above, low frequency changes or variables indicative of afavorable response to pacing include but are not limited to: eithertemporally earlier or more synchronous shortening of the paced region;increases in longitudinal or radial displacement of the mitral valveannular region; increases in peak acceleration or velocity oflongitudinal or radial displacement of the mitral annular region (S1 orS2 peak). The change in radial and longitudinal shortening may reflectthe ejection fraction, a variable correlated with outcome in heartfailure. The position of the LV wall as determined by the sensor maydetermine the effects of pacing on LV volume (See FIG. 20). Midfrequency indices or variables associated with improved LV functioninclude but are not limited to: steepening of the slope or an increasein the peak amplitude of the isovolumic contraction phase; shortening ofthe isovolumic contraction time interval; shortening in the isovolumicrelaxation time interval; increases in the LV filling time relative tothe cardiac cycle length; increases in the time of aortic valve closureor mitral valve opening from QRS onset divided by the cardiac cyclelength; increases in the systolic ejection phase time interval;increases in the time from QRS onset to aortic or pulmonic valveclosure; and increases in the time from QRS onset to aortic or pulmonicvalve closure divided by the cardiac cycle length. Changes in LVfunction indicative of a favorable response to pacing at the highfrequency range would be a reduction in mitral valve regurgitationamplitude and duration as well as a frequency change. Lastly, themyocardial performance index may be also utilized as a measure of LVfunctional response and the same may be determined from mid-frequencysignals or a combination of mid- and low-frequency signals.

Pacing of certain regions may not produce improvements in LV function.Ischemic regions may not respond to pacing or may contract poorly due tothe presence of non-contractile tissue and may therefore be avoided. Itshould also be noted that the displacement and the related strain ratecan be used to diagnose areas of ischemia, which may also be useful inoptimizing CRT, such as by avoiding the pacing of these regions. As anexample, regions where shortening is delayed or disappears under stressconditions, e.g., increased oxygen demand, such as dobutamine infusion,are likely due to ischemic blood flow. Other factors, such as theability to electrically couple to the region, may affect pacing. Pacingcapture thresholds must be determined, which could occur by increasingthe pacing stimulus and measuring the displacement, which is shown inFIG. 26. In particular, curves 584-592 represent pacing signals from 0.5mV to 3.0 mV. Curve 584 shows a small shortening, curve 586 shows more,and curve 588 shows still more. However, no difference in shortening isseen between curve 588 and curve 592, thus the optimal capture thresholdcan be determined to be 2.0 mV. Interval timing such as simultaneousventricular pacing, RV first pacing, or LV first pacing, may also needto be optimized to produce the desired response.

LV motion sensing with an acceleration sensor primarily at low frequencymay allow the identification of candidates for CRT. Many patients with alow ejection fraction and history of ischemic heart disease undergo theimplantation of a defibrillator. During the defibrillator placement, acandidate for CRT could be identified and an LV lead placed, thuspreventing the exposure of the patient to two separate procedures.

One way to assess candidates for CRT is by assessing contractilereserve. The presence of shortening during diastole is indicative ofcontractile reserve. The difference in peak ejection velocity orshortening or the start of motion or shortening in any two regions,e.g., the septal to posterior region or the posterior to lateral region,is indicative of dyssynchrony that may respond to therapy. Thesedifferences may be based on the time from onset of systole for eachregion or may be the direct difference between two regions. Thus, adifference in peak velocity from the septal to posterior wall of greaterthan 50-100 ms may indicate a target pacing region of the posteriorwall. Septal motion could be detected by a sensor located in the RA/RVor near the opening to the coronary sinus or near the posteriorinterventricular vein branch. Specific displacement patterns, such asboth shortening and lengthening, that occur between QRS onset and aorticvalve closure (FIG. 23), are indicative of dyssynchrony. These delays inregional shortening, post-systolic shortening, and dyssynchronouscontraction patterns, may be present regardless of QRS duration andhence can be used to identify candidates and responders even if the QRSis normal or only modestly widened.

To accomplish target pacing region identification, characterization,pacing optimization, and to identify candidates for CRT as describedabove, a myocardial motion mapping system may be employed (FIGS. 25, 27and 28). This system shows a multi-sensor, multi-electrode motionmapping catheter system 594. An acceleration sensing device, such as acatheter, LV lead, guidewire, guide catheter/catheter system, or acombination thereof, is used as a mapping device by positioning thedevice in various locations of the coronary sinus and LV vasculature(FIGS. 22 and 23). If desired, the acceleration sensing devices may beplaced in the ventricular chambers, preferably the LV. If a single ortwo axis sensing is used, the catheter can be rotated until the optimalsignal is detected. This may occur when at least one sensor is parallelto the axis of motion. Marker bands on the catheter could indicate theappropriate sensor orientation during the procedure or reference pointsas described previously could be used. Alternatively, 4-axis sensingcould be employed using two dual axis sensors as described above. Inthis configuration, three of the four axes are used to measureacceleration in the x-, y-, and z-orientations for 3-axis sensing andthe fourth channel may be used for sensing vibrational motion andvalvular events or pathology. Alternatively, 6-axis sensing with threeperpendicular dual axis sensors could be employed with three axes usedto detect displacement motion and three axes used to detect vibrationalmotion. The acceleration sensing device could be guidewire directed orsteerable, including tip deflection. Steerability is accomplished byhaving one-to-one, or as substantially close to this as possible,torqueability which can be accomplished with a braided catheter design.Tip deflection can be accomplished with wires 596 that run the length ofthe device and are affixed to the tip 598 (FIG. 27). A lever 602 in thehandle 604 of the catheter pulls the deflection wires 596, producingdeflection at the tip 598. Steerable deflection devices are familiar tothose skilled in the art. One or more sensors 606 and pacing electrodes(see FIG. 28) may be located immediately adjacent to each other or thepacing electrode may be located between the sensors. The region of thesensor in the mapping catheter may be highly flexible as described aboveto ensure that the sensors move in concert with the myocardium. Thecatheter 594 may further be equipped with a connector 608 that includesa hub 626 and a plurality of connectors 628, which may includeacceleration input connectors and electrode pacing connectors, that mayconnect to an microprocessor-based display system (see FIG. 28)including a manifold 632.

Referring to FIG. 28, the system 594 may further include a guidewireinsertion port 634 for guidewire 636, an optional port for contrastinjection 638 with an accompanying contrast port 646, an optional portfor balloon inflation and deflation 642 coupled to an optional venogramballoon 644. Also included are, e.g., three sets of sensor pairs 646,648, and 652, and three sets of electrodes 654, 656, and 658. Thesensors may be, e.g., 5-10 mm apart.

Referring to FIG. 28, the mapping acceleration sensing device 594 may bedirectly connected to a microprocessor-controlled display 612 thatpresents motion signals as acceleration 614, velocity curves 616, strainrate curves 618, and displacement curves 622, or some combination of thethree, with ECG data 624. The catheter and acceleration signal can alsobe input into a cardiac electrogram data acquisition system as may bealready used by the physician. The acceleration signal may be displayedas a voltage, similar to the cardiac electrogram. The onset of motionsignals may be easily displayed and compared to the surface ECG orintracardiac electrogram. Other reference points, as disclosed earlier,such as isovolumic contraction or valve closure, may also be displayed.(FIG. 25). The mitral valve regurgitation signal may further bedisplayed.

Also shown in FIG. 28 is close-up display 660, containing curves662-666. These curves display displacement data corresponding to thethree pairs of acceleration sensor data for mechanical mapping. In thesefigures, shortening is exhibited by a negative deflection.

Additionally, the mapping acceleration sensing device may be used tofacilitate coronary sinus access and cannulation of LV vein branchesthat feed into the coronary sinus, necessary steps in the mappingprocess and LV lead implantation. One method to achieve access to thecoronary sinus is conducted by dragging the mapping device from the AVnode superiorly along the base of the RA, the interatrial septum, or themedial RA wall. When the device moves over or is near the coronary sinusostium, the flow of blood from the ostium into the RA causes the deviceand/or tip to deflect or vibrate. The deflection or vibration may besensed by the acceleration sensor. In addition, once the device is inthe coronary sinus, it can be dragged or pushed along the inferior orlower border of the sinus. LV veins are detected by deflection orvibration by the sensor as it passes over the ostia, or branches, of theveins that drain into the coronary sinus. Alternatively, Doppler flowcrystals and MEMs pressure sensors, and anemometry flow sensors may beused for coronary ostium identification and LV vein branches. Thesesensors may also be combined with the acceleration sensor.

In one embodiment, motion signals may be derived from serial, orvarious, combinations of the sensors or sensor pairs, at a knowndistance of separation, e.g., 5-15 mm, and may provide multiplevelocity, displacement, and strain rate curves synched with a signalrelated to the start of systole such as single QRS or a contractionstimulus, or isovolumic contraction or mitral valve closure (FIGS. 23and 28). Systole may also be induced by a separate pacing catheterconductively coupled to the RA or RV septum. Regions of late motiononset relative to the onset of systole, determined by the R wave of theECG, septal activation on the EGM, or mitral valve closure, may beidentified. Also, regions of post-systolic shortening relative toisovolumic relaxation or aortic valve closure or the t-wave may beidentified. These late and post-systolic shortening regions maysubsequently be paced by electrodes between the sensors that identifiedthe late motion onset to elicit earlier activation. A new set ofdeformation curves may then be analyzed to confirm that the region ofearly activation pacing produces a more synchronous deformation.Further, the mid-frequency sensor measures the change in peakacceleration or velocity during the pacing of the identified targetregion, confirming a positive response to pacing (FIGS. 23 and 29). LVfunctional responses such as the myocardial performance index could alsobe measured during the test pacing (FIGS. 25 and 29).

Referring in more detail to FIG. 29, a chart is shown which may be usedto identify regions of late deformation and for assessing various othervariables related to performance. Curve 668 shows the ECG signal, curve672 shows the acceleration signal, where the left-most point is the zeropoint established by the QRS, “EP” refers to the ejection phase, “E”refers to early diastolic filling, “A” refers to atrial contractionfilling, time interval “A” measures the start of IVC to the end of IVR,and time interval “B” measures the time interval of the EP. MPI=(A−B)/B.Curve 674 shows the acceleration signal from region #1, showing inparticular the IVC time interval 676 and the peak IVC signal 678, aswell as the delayed mechanical shortening 682 in the target pacingregion. Referring to FIG. 30, an alternative mapping strategy may alsobe employed in which a simplified catheter with only a 1, 1 pair sensor,i.e., perpendicular to each other, or 3 sensors, each perpendicular toeach other, uniaxial, biaxial, or triaxial, is positioned in various LVand LV locations, e.g., septal to lateral in the coronary sinus andgreat cardiac vein). One sensor or sensor pair detects both the onset ofsystole or diastole, e.g., isovolumic contraction or relaxation; oraortic or mitral valve closure, and regional motion, or one of twosensors or one of two sensor pairs may be utilized to detect the sameonset of systole or diastole and the other sensor or sensor pair detectsthe regional motion. Alternatively, 3 axes of a dual axis pair may beused for displacement sensing and the 4^(th) axis may be used forvibration sensing. Alternatively, 3 axes of a 3-sensor device may beused for sensing displacement motion, and the other 3 axes may be usedfor sensing vibrational motion. No electrodes, one electrode, or twoelectrodes may be employed.

The regional motion from each location is recorded and stored anddisplayed. The motion at each location is compared against the QRS orendocardial pacing signal or the other systolic and diastolic referencepoints. The region of latest motion relative to the reference point isidentified and the lead is positioned to the same anatomical location.It should also be noted that epicardial mapping may be performed duringopen chest or minimally invasive procedures using the same principlesand sensors as above and appropriate device designs.

In another mapping strategy, a roving electrode (e.g., a guidewire) canbe positioned in various locations of the LV venous system and RVchamber and a test pacing stimulus applied to the myocardium. Referringto FIGS. 24 and 31, a guidewire 684 with an uninsulated region orelectrode region 686 may be connected to a pulse generator via connector688 and unipolar pacing may be performed. The guidewire may also havetwo uninsulated regions or two electrode regions for bipolar pacing. TheLV functional effects of the test pace can be measured by anacceleration sensor or a dual axis sensor pair perpendicular to eachother. The sensor or sensors may reside on a coronary sinus guidecatheter 692 (see FIG. 32) or on a catheter 700 within the lumen withinthe coronary sinus guide catheter 692 (see FIG. 33). The catheter 700may further have a pacing guidewire port 702 to accommodate guidewire684.

For example, the sensors 694 may reside on catheter 690, and may bebattery powered via battery 698. The sensors may number one, two, orthree, each perpendicular to the others, and may have outputscorresponding to a low-frequency (<20 Hz) signal 704, a mid-frequency(20-150 Hz) signal 706, and a high-frequency (>150 Hz) signal 708.

In this way, and referring to FIG. 34, the mapping system 710 is made ofthe acceleration sensing catheter 700 and the pacing guidewire 684. Thepacing guidewire may be powered by a pulse generator 712.

The output of the sensors may be connected to a signal conditioningmodule and battery power module 714 prior to input into the electrogramrecording 716 and display device 718. The output of the signalconditioning module may be analog signals if the electrocardiogramdisplay is to be used. The signal conditioning module may also be usedto correct or zero out the effects of gravity and the related tiltsignal. Output from the signal conditioning module may also be digital.A microprocessing chip in the conditioning module may also performfunctions such as forming a composite signal from multiple orientationaxes and integration. The catheter within the guide catheter may have aguidewire lumen through which a pacing guidewire may be used to testpace target sites. This catheter may also have a port for contrastinjection and may additionally have a balloon to perform an occlusivevenogram.

The sensor catheter 700 may also have a curved tip (e.g., with a90-degree bend) to facilitate access to tributary veins of the coronarysinus and great cardiac vein. The sensor catheter within the coronaryguide catheter could also be moved from septal to lateral within thecoronary sinus and great cardiac vein to identify general regions ofdyssynchrony. The pacing wire could then be directed to the tributaryveins of the coronary sinus or great cardiac veins or to the generalregion of delayed onset displacement motion. Variables such as the timefrom QRS onset to aortic valve closure (increase), peak accelerationduring isovolumic contraction (increase), the length of the isovolumiccontraction time interval (decrease), may be measured and are indicativeof a favorable or therapeutic response and a more optimal LV or RVpacing region (FIG. 25). The changes in time intervals of LV cycle(e.g., LV filling time) may be normalized by dividing by the cardiaccycle length or the square root of the cardiac cycle length or by someother method. Other measures of LV function as sensed by theacceleration sensor may be utilized including favorable changes in themitral regurgitation signal. The myocardial performance index(isovolumic contraction time plus the isovolumic relaxation time dividedby the ejection time) may also be used as a performance indicator withdecreases in indicator viewed as more favorable. When a region ofimproved LV function is identified, the pacing guidewire is left inplace and the CRT LV lead is inserted over the pacing guidewire to thetarget pacing region.

Some patients may respond with favorable LV mechanics with only RVpacing if it is performed in the correct location. The optimal RV siteto maximize LV function can be identified in the mapping strategy above.The acceleration sensor may reside in the coronary sinus while the RVpacing site is identified. This may eliminate the need for an LV lead insome patients.

Alternative embodiments are apparent from the above description such asseparating the higher frequency sensing accelerometer from themyocardial motion sensing accelerometer. Thus, referring to FIGS. 35 and36, a system is shown for identification of the target pacing region andoptimizing and characterizing the pacing response. The higher frequencysensing accelerometer may be incorporated into an LV lead or coronaryguide catheter 724 or guidewire (see guide catheter 724 of FIG. 36).Guide catheters and guidewires are commonly used in CRT procedures. Theacceleration sensor 726 on the guide catheter 724 may reside in theright atrium, at the coronary sinus ostium, or within the coronarysinus. The guide catheter 724 may be curved to facilitate access of thecoronary sinus. Additionally, valve closure sensing may be performedexternally with an acoustic sensing device.

The remainder of the system may be the mechanical mapping catheter 722,which includes a guidewire lumen 728 with ports 732 and 734, a pacingelectrode 736, acceleration sensor 738, e.g., one that is perpendicularto the catheter's longitudinal axis, an optional acceleration sensor742, an electrode connector 744, and a sensor connector 746. Thecatheter 722 may be angled to facilitate LV vein cannulation. FIG. 37shows one potential arrangement of sensor 738 and guidewire lumen 734.Alternatively, as shown in FIG. 38, an electrode 736′ may be disposed atthe distal tip of the catheter 722 while a sensor 738′ is disposedproximal thereof.

Thus, in still another embodiment, and referring in particular to FIGS.39 and 40, an acceleration sensor 752 for mid- to high-frequency sensingof the onset of systole and diastole and mitral regurgitation may beincorporated into a coronary sinus guide catheter 750. A set ofconductive elements 748 for the sensor 752 may be coupled to a connector754 that is used to connect to the microprocessor display.

A myocardial motion sensing accelerometer 746 is incorporated into amapping catheter or LV lead 760. In the LV lead design, the conductiveelements 754 for the low-frequency myocardial motion accelerometer 746may be coupled to a proximal lead connector 758. The connector of thelead may be compatible with typical CRT IPGs (e.g., IS-1), although thisis not necessary; in fact, the sensor connector and sensor signal may bedesigned to generally not interfere or even be read by the CRT IPG.Element 762 indicates the CRT pacing and sensing connector area.Connector 756 is also shown, which indicates a removable LV leadaccelerometer connector for signal display.

Placement of the catheter is shown in FIG. 39, relative to the coronarysinus 770 and the coronary ostium 780. An optional pacing electrode 764is shown, as well as guidewire, which may employ an integrated sensorfor low-frequency myocardial motion sensing in the manner of FIG. 24.

During placement, the lead connector may be coupled to the accelerationsensor microprocessor display for visualizing myocardial motion signalsand optimizing the LV lead placement. Alternatively, the LV lead sensormay be conductively coupled to a removable connector in the proximallead portion, thus allowing the measurement of myocardial motion duringlead placement. The LV lead sensor connector may also be capped aftermapping and for long-term implantation. Alternatively, the sensors inthis design may be RF MEMs accelerometers that are inductively-poweredand which wirelessly transmit the data, thereby eliminating the need forconducting wires or elements.

FIG. 40A shows an embodiment of a guidewire-mounted sensor for use withthe above guide catheter. In particular, guidewire 766 may have at adistal tip a soft tip 774, adjacent to which is a flexible coil section768, within which is a sensor 772.

FIG. 40B shows an embodiment of an alternative LV lead design 790 ormapping catheter which may be used with the above guide catheter. LVlead 790 has at a distal tip a flexible coil 768′ which terminates at adistal tip in a soft tip 774′. Within the flexible coil 768′ is a sensor772′. Electrode 776 may be provided adjacent to but proximal of theflexible coil 768′.

Referring to FIGS. 41-44, another alternative mapping device system andmethod for optimizing and identifying a target pacing region may includea venous guide sheath, a double lumen pacing catheter, and anacceleration sensing guidewire. The system also identifies the coronaryostium and coronary sinus vein branches using the accelerometer sensor.

A venous sheath 838 is used to gain access to the right atrium (“RA”)via the subclavian or femoral vein. This sheath may include an optionalmid- to high-frequency acceleration sensor 842. The sheath may haveappropriate bends to facilitate entry into the coronary sinus.

A sensing guidewire with one or more sensors 792, 794, at least onebeing a lower-frequency sensor disposed on a highly flexible tip 796(e.g., a coil tip 796), is placed into the RA via the sheath. Thelower-frequency sensor may be multi-axis. An optional additional sensormay also be provided to sense low or high frequencies. The distancebetween the sensors may be, e.g., 5-10 mm. The sensor guidewire 800 isused to identify the coronary ostium (as above) by detecting the flow ofblood into the RA and is then inserted into the coronary sinus. Theguidewire 800 is shapeable or may have a slight bend 798 in the distalregion, e.g., a 135 degree bend. The sensor guidewire 800 can then bepositioned along the coronary sinus and into the LV veins for measuringmyocardial deformation and velocity and comparing it to the referencepoint signal, i.e., vibrations related to isovolumiccontraction/relaxation and/or valve closure, provided by the guidesheath sensor. Alternatively, a double lumen catheter 802 may bepositioned into the RA or coronary sinus over the sensor guidewire 800and an optional higher frequency sensor 804 on this device is used toprovide reference signals.

The sensing guidewire 800 maps regions of late deformation, and mayfurther include an electrical connector 806 and an optional proximalsensor 808 for sensing perivalvular events.

The double lumen pacing catheter 802 contains two guidewire lumens 812and 814, lumen 812 serving as a guidewire sensor lumen and lumen 814serving as a coronary wire sensor lumen, with openings in the distal tip816, a pacing electrode 818, an optional coronary sinus occlusionballoon 822 with inflation port 824 for obtaining a venogram, optionalacceleration sensors 804, such as for measuring high frequency signals,and the same may also be steerable. The overall diameter may be, e.g.,2-3 mm. Referring in addition to FIG. 43, a hub 826 may be provided witha sensor guidewire port 828, a coronary wire port 832, a high-frequencysensor connector 834 coupled to conductors within a lumen 834′, and anelectrode connector 836 coupled to conductors within a lumen 836′.

The double lumen pacing catheter is placed in the coronary sinus overthe sensing guidewire. The venous guide sheath may be advanced into theostium prior to double lumen catheter placement or LV lead placement.The balloon of the double lumen catheter may be inflated and a venogramobtained by injecting contrast though one of the catheter's lumens.After a target pacing region is identified in an LV vein with the sensorguidewire, the double lumen pacing catheter is advanced over the sensorguidewire to the region. Pacing is conducted with the double lumenpacing catheter and optimization of the target pacing site and intervalsis carried out. A second guidewire for the LV lead is then advanced downthe second lumen of the double lumen pacing catheter and into the targetregion. The pacing catheter and sensor guidewire are then removed,leaving the lead guidewire in place. The LV lead is then positioned intothe target region over the second guidewire. With the double lumenconfiguration, the sensor guidewire can be made larger and moremaneuverable without limiting the ability to place a small over-the-wireLV lead in the target region.

Myocardial motion mapping would be ideal for LV pacing that involvesmultiple electrodes. CRT may be optimized by pacing and early activationof all late deforming LV sites. Deformation mapping may identify theseregions and then guide the placement of electrodes in the areas for CRT.Alternatively, if the mapping catheter is also the LV CRT lead, then themapping lead may be left in the optimal location and connected to theIPG.

In the above catheter and implantable embodiments, miniaturization ofthe sensor is critical and wafer or die scale packaging of the sensorcomponent is preferred. Consequently, where the MEMs sensor is attachedby conductive elements to a connector and then to a microprocessorand/or display device, specific designs for attachment of the conductiveelements to the silicon substrate of the wafer package chip must beutilized. It is particularly important to minimize the number ofconductive elements that require attachment to the acceleration sensor.Potentially, at least 5 connections are required for a 3-axis sensor;however, using multiplexing circuitry or averaging the signal from allthree sensors can eliminate two wires thus reducing the connections tothree. In one embodiment, solder balls are integrated into the sensordie. A flex circuit with bonding pads that aligns with the solder ballsis used for attachment to the die. The bonding pads of the flex circuitare in electrical communication with conductive elements that are usedto attach to connectors at the proximal end of the catheter. The diepart is flipped onto the bonding pad, which is heated to allow the flowof the solder and bonding of the die to the flex circuit.

Alternative methods for conductive element attachment of MEMs sensorsare provided in, e.g., U.S. Pat. No. 5,715,827 for a pressure sensor.FIGS. 45-46 show one potential embodiment to accomplish attachment foran acceleration sensor. The sensor chip 840 has an elongated siliconsubstrate 842. V or U-shaped via wells 844 are etched using siliconetching techniques into the elongated substrate 842. The wells 844 runthe length of the elongated substrate 842 and abut against semiconductoroutput connectors 846 from the acceleration sensor integrated circuitry848. Usually a sensor has three connectors: one for power, one forground, and one for output. Additional connectors may be used for eachaxis output. A single output connector with a multi-axis sensor may havecircuitry for multiplexing each axis output. Alternatively, the outputmay be an average or composite of the different axes. Hence three wellsare etched and made continuous with the sensor circuitry for power 852,ground 854, and output 856. The silicon substrate well bottom and wallsare doped to provide conductivity. The wells are then coated with metal858 through a sputtering process or via other such processes. Forexample, a sputtered chromium and gold coating may be used. Theuninsulated terminal length of small gauge copper wires 862 (e.g., 48AWG) or a doped polymer flexible connector is then soldered to thewells. An epoxy or glass lid 864 or other such material, such as a waferor polymer cap, may be bonded to the top of this chip/wire hybrid toprotect the structure from damage. These wires or conductive polymersare now conductively coupled to the chip sensor and can be extended downthe length of a catheter component and attached to a connector that willplug into a microprocessor data acquisition component.

FIG. 47 shows a circuit diagram of a system that may be employed inembodiments of the invention. In particular, FIG. 47 shows a pin layoutfor a sensor chip that may be employed, along with the x-, y-, andz-outputs from the sensor chip.

FIG. 48 shows a portion of a flexible circuit board that may employ thesensor chip. The sensor chip is mounted on the left side of the board,which is the portion that enters the patient. Capacitors C1-C5 areemployed and are disposed directly adjacent the sensor chip as may beseen.

As noted above, the general design of the accelerometer sensors measurescapacitance changes due to the movement of a proof mass beam with a sidearm interdigitated between two capacitor plates. As the proof mass beamand side arm move with acceleration or vibration, the capacitancechanges and this signal can be output as a measure of motion.

In this way, the sensor chip can measure extremely small changes incapacitance and thus acceleration. One of the functions of capacitorsC1-C5 is to decouple certain voltages so that only signals from thesensor chip are registered at the signal analysis system (another is toprovide the circuitry for the passband so that only a certain bandwidthof signals are passed). To ensure that a minimum of stray noise voltageis picked up by the conductive leads, capacitors C1-C5 are disposed asclose to the chip as is practical, so that the signal travel distance isas short as possible.

It should be noted that the description above refers to specificexamples of the invention, but that the scope of the invention is to belimited only by the scope of the claims appended hereto.

1. A device for monitoring cardiac function, comprising: a. At least oneacceleration sensor for disposition within or on a patient's heart; b.Wherein the acceleration sensor includes means for sensing bothvibrational and displacement motion frequencies.
 2. The device of claim1, wherein the acceleration sensor is designed to detect vibrationalfrequencies between about 20 Hz and 150 Hz and displacement motionfrequencies less than about 20 Hz.
 3. The device of claim 1, wherein theacceleration sensor is designed to detect vibrational frequenciesrelated to mitral regurgitation greater than about 150 Hz.
 4. The deviceof claim 1, further comprising a circuit implemented in hardware orsoftware, or both, for mathematically integrating the displacementmotion acceleration signals.
 5. The device of claim 1, wherein thesensor is implemented within or on a catheter, and wherein the catheteris structured and sized such that the same may be disposed in the veinsof the left ventricle of the patient's heart.
 6. The device of claim 1,wherein the sensor is a MEMs capacitive acceleration sensor.
 7. Thedevice of claim 6, wherein the sensor further comprises an integratedinductive coil.
 8. The device of claim 1, further comprising at leasttwo acceleration sensors disposed within or on a patient's heart,wherein each sensor includes means for sensing both vibrational anddisplacement motion frequencies.
 9. The device of claim 8, wherein theat least two acceleration sensors include two or three dual-axissensors, having four or six axes for motion sensing, and wherein thesensor axes are disposed in a perpendicular fashion to one another. 10.The device of claim 9, wherein for four axes for sensing, three are formotion sensing of the heart in three orientations, and the fourth is forhigh frequency sensing; and wherein for six axes for sensing, three arefor motion sensing of the heart in three orientations, and three are forhigh frequency sensing.
 11. The device of claim 10, wherein the highfrequency sensing is to monitor changes in mitral regurgitation.
 12. Thedevice of claim 1, wherein the sensor is disposed on an endovascularcatheter.
 13. The device of claim 12, wherein the endovascular catheteris a guide catheter or a coronary sinus catheter.
 14. The device ofclaim 13, wherein the endovascular catheter is a coronary sinuscatheter, and further comprising an occlusion balloon coupled to thecatheter.
 15. The device of claim 13, wherein the endovascular catheteris a coronary sinus catheter, and further comprising a pacing electrodecoupled to the catheter.
 16. The device of claim 1, wherein the sensoris disposed on a guidewire.
 17. The device of claim 1, wherein thesensor is disposed on an LV lead.
 18. The device of claim 12, furthercomprising a coronary stenting device removably mounted to theendovascular catheter.
 19. The device of claim 7, further comprising acoronary stenting device removably mounted to an endovascular catheteron which is also mounted the sensor, wherein the inductive coil isintegral to the stenting device.
 20. A method for identifying CRT pacingregions, comprising: a. Placing an acceleration sensing device in apatient's heart; b. Sensing acceleration signals at one or morefrequencies; c. Comparing the sensed acceleration signals to a referencepoint indicative of the start of systole or diastole.
 21. A method formonitoring cardiac function, comprising: a. Placing at least twoacceleration sensing devices in a patient's heart; b. Sensingacceleration signals at two or more frequencies.
 22. The method of claim21, wherein the cardiac function monitored corresponds to post-systolicshortening.
 23. A method for monitoring cardiac function, comprising: a.Placing at least two acceleration sensing devices in a patient's heart;b. Sensing acceleration signals at one or more frequencies; c. Whereinone of the devices measures vibrational motion and another measuresdisplacement motion.
 24. The method of claim 23, wherein at least onesensing device detects myocardial vibrations indicative of isovolumiccontraction or relaxation or valve closure and wherein another detectsmyocardial displacement.
 25. A method for identifying CRT pacingregions, comprising: a. Placing a sensing device in a patient's heart;b. Pacing target pacing regions with a pacing device; c. Measuringsignals corresponding to heart function; d. Placing a CRT lead is aregion where the pacing causes a favorable change in the heart functionsignal.
 26. The method of claim 25, wherein the heart function signal isthe myocardial performance index.
 27. A method for identifying CRTpacing regions, comprising: a. Placing an acceleration sensing device ina patient's heart; b. Pacing target pacing regions with a pacing device;c. In response to the pacing, measuring acceleration signals indicativeof LV function.
 28. The method of claim 16, wherein the signalsindicative of LV function include the time intervals of the LV cyclephases, the peak amplitude of the LV cycle phases, signals related tomitral regurgitation, the time from QRS onset to aortic or pulmonicvalve closure, the length of isovolumic contraction, the diastolicfilling time, the peak acceleration, velocity, or shortening duringisovolumic contraction, the myocardial performance index, andcombinations of the above.
 29. The method of claim 16, wherein thedevice is placed in one of the left ventricular veins.
 30. A method foridentifying CRT pacing regions, comprising: a. Placing an accelerationsensing device in a patient's heart; b. Sensing acceleration signals atone or more frequencies; c. Identifying regions of late onset of motionfrom the sensed acceleration signals; d. Wherein said regions of lateonset of motion are the CRT pacing regions.
 31. The method of claim 30,further comprising disposing electrodes from a pacemaker device near oron the regions of late onset motion.
 32. A method for identifyingcardiac features, comprising: a. Placing an acceleration sensing devicein a patient's heart, the device including a catheter with anacceleration sensor disposed at or near the distal tip of the catheter;b. Moving said device in proximity to a cardiac feature; c. Sensingsignals corresponding to vibration or deflection due to blood flow fromthe cardiac feature.
 33. The method of claim 32, wherein the cardiacfeature is the coronary ostium or a vein branch.
 34. The method of claim32, wherein the sensing is performed using Doppler ultrasound, a MEMspressure sensor, or an anemometry device.
 35. A device for monitoringacceleration of tissue in a human body, comprising: a. At least oneacceleration sensor chip for disposition within or on a tissue in apatient; b. A flexible circuit mounted to said sensor chip for carryingsignals from said sensor chip to a signal analysis unit; c. At least onecapacitor disposed on the flexible circuit adjacent said sensor chip fordecoupling or attenuating noise voltages such that the signal to noiseratio of signals from said sensor chip to reach the signal analysis unitis higher than in the absence of said at least one capacitor.